Functional divergence of somatotropic axis genes in rainbow trout (Oncorhynchus mykiss): structural organization, regulation and physiological roles

Abbreviations and terms:

gh1; gh2 – growth hormone genes

igf1; igf2 – insulin-like growth factor genes

ghr1; ghr2 - growth hormone receptor genes

sst – somatostatin gene

GH – growth hormone protein

IGF-I; IGF-II - insulin-like growth factor proteins

SST – somatostatin protein

GHBP – growth hormone binding protein

IGFBP - insulin-like growth factor-binding protein

IGFR1A; IGFR1B - insulin-like growth factor receptors

GH-IGF - growth hormone-insulin-like growth factor axis

Introduction

The rainbow trout, a member of the Salmonidae family, holds significant economic, social, and scientific importance (Dysin et al., 2022; FAO, 2024). Consequently, investigating the genetics of rainbow trout is a critical step toward developing more productive breeds with genetically determined adaptive traits (Blay et al., 2021; Shcherbakov et al., 2023). In this regard, genes within the somatotropic axis are particularly promising due to their roles in growth rate, body conformation, metabolic processes, immune response, and osmoregulation. Circulating levels of growth hormone (GH) and insulin-like growth factor I (IGF-I) remain among the most reliable growth indicators throughout vertebrate evolution (Pérez-Sánchez et al., 2018; Chandhini et al., 2021; Izutsu et al., 2022).

The core components of the GH-IGF axis include ligands such as growth hormone paralogs 1 and 2 (GH1, GH2), insulin-like growth factors I and II (IGF-I, IGF-II), and somatostatin (SST). Receptors involved include growth hormone receptors 1 and 2 (GHR1, GHR2), duplicates of the IGF-1 receptor (IGFR1A, IGFR1B), as well as transport proteins that bind GH and IGFs (GHBP and IGFBP, respectively) (Reindl et al., 2012; Canosa et al., 2020).

Considerable progress has been made in elucidating the function of the somatotropic axis. Current research focuses on the paralogs of growth hormone, insulin-like growth factors, and other axis components to understand their capacity to act as genetic backups and to perform diverted or specialized functions (Kamenskaya et al., 2015; Cleveland et al., 2018). Promising directions include studying physiological processes through tissue-specific gene expression analysis of the somatotropic axis and understanding its regulation by environmental conditions and epigenetic factors (Zhang et al., 2022). A detailed understanding of the molecular mechanisms governing the somatotropic axis, the interactions among its genes, and the influence of various internal and external factors is fundamental for devising genetic strategies aimed at enhancing growth performance and adaptive capabilities in rainbow trout (Yue et al., 2014; Tyshchenko et al., 2024).

This study aims to conduct a comprehensive literature review on the functional role of the growth hormone gene in the biological and molecular processes of rainbow trout, with particular emphasis on its interactions within the GH-IGF somatotropic axis.

Material and methods

Literature was identified using open-access scholarly search engines, including Google Scholar (scholar.google.ru), PubMed (pubmed.gov), and Semantic Scholar (semanticscholar.org). The academic networking platform ResearchGate (researchgate.net) was additionally used to obtain articles directly from authors. Relevant studies were also located through in-text citations and reference lists of the examined publications. The final dataset comprised 111 articles published over the past 40 years, including 69 published within the last decade, 47 of which appeared in the past five years.

Bioinformatic data were retrieved and analyzed using the NCBI (ncbi.nlm.nih.gov) and Ensembl (ensembl.org) databases. These data were used to construct the scheme «Comparison of the gene structures of gh1 and gh2 in rainbow trout» and the table «Pairwise comparison of coding and non-coding regions of gh1 and gh2 genes in rainbow trout» presented in first chapter. Data visualization for schematic representations was performed in Python using the Matplotlib library. Sequence analyses and pairwise alignments were conducted in Python with the Bio.pairwise2 module within the PyCharm Community Edition environment (version 2025.1).

The schematics «Figure 2. Schematic representation of the effect of modulated circadian rhythms...» in subsection 2.1 and «Figure 3. Dynamic equilibrium of the GH–IGF axis during rainbow trout adaptation to seawater» in Subsection 2.2 were generated using the online diagramming platform Draw.io (drawio.com).

1. Structure of growth hormone genes in rainbow trout

Growth hormone, also known as somatotropin, is a highly conserved protein. Its molecular mass, amino acid composition, and biochemical, physicochemical, and immunochemical properties are remarkably similar across different animal taxa (Hayashida et al., 1975). This similarity reflects deep evolutionary conservation, which is further supported by phylogenetic studies in fish showing that the genes encoding growth hormone, prolactin, and placental lactogens originated from a common ancestral gene whose structure has been retained in the sea lamprey (Petromyzon marinus) (Chen et al., 1994; Li et al., 2014). These findings suggest that growth hormone represents one of the most ancient regulatory factors in vertebrate development.

In rainbow trout, two distinct forms of somatotropin were first isolated from the pituitary gland by Agellon et al. (1988), which allowed the determination of their molecular structures and amino acid sequences. The emergence of the second paralog, gh2, along with other duplicated genes, is associated with a whole-genome duplication event that occurred during the evolutionary history of the Salmonidae family (Allendorf et al., 1984). According to the genome assembly O. mykiss (USDA_OmykA_1.1, Arlee line, USA), the gh1 gene is located on chromosome 12, spans 4,135 base pairs, and consists of six exons and five introns. The gh2 gene is located on chromosome 13, slightly shorter at 3,615 base pairs, but exhibits a structure analogous to that of gh1 (Fig. 1).

Figure. 1. A comparative analysis of the structure of the growth hormone genes gh1 and gh2 in rainbow trout. Both genes have an identical number of exons, which are highlighted by rectangular boxes. The scale bar along the axis shows the linear length of gh1 and gh2 from the 5' end to the 3' end. Similar nucleotide sequences are shown in green. Areas that differ from, or are not found in, the gh1 gene sequence compared to the gh2 gene, and vice versa, are highlighted in red. Data visualisation was performed in Python using the Matplotlib library.

 Sequence alignment of gh1 and gh2 using the Needleman–Wunsch algorithm revealed 84.0% overall nucleotide identity (Altschul et al., 1997). Pairwise comparison of exon and intron regions shows variable percentages of sequence similarity (table 1).

Table 1. - Comparison of coding and non-coding regions of the gh1 and gh2 genes in rainbow trout. Analysis and pairwise alignment of sequences were performed in Python using the Bio.pairwise2 library.

As shown in Figure 1 and Table 1, the gene organization of gh1 and gh2 is largely conserved, though they differ in length and in the identity of certain segments. Exons 2–5 display high conservation, averaging 96% sequence identity, which is typical for coding regions of paralogous genes. These regions likely preserve amino acid sequences and protein functions (Kamenskaya et al., 2017). Exon 6 shows moderate conservation (82%), likely due to the presence of noncoding terminal regions that are nonhomologous between the genes. The first exon of gh2 is notably shorter than that of gh1, resulting in lower sequence identity. The significant truncation of exon 1 in gh2 may have involved mobile genetic elements and could reflect adaptive restructuring that endowed gh2 with modified or novel physiological functions, possibly through compensatory mechanisms (Hu et al., 2023; Mallik et al., 2025). The intron identity percentage varies considerably (40–80%), as introns are generally less conserved, leading to distinct or nonhomologous intronic sequences between gh1 and gh2.

Both gh1 and gh2 genes produce a single mRNA transcript with one splicing variant. The gh1 gene encodes a protein composed of 260 amino acid residues, while gh2 encodes a shorter polypeptide of 210 residues (ensembl_O.mykiss_gh1; ensembl_O.mykiss_gh2). Thus, despite their close evolutionary relationship, the two genes produce protein products that likely differ in their functional roles.

Genomic features regulating gh paralogs

Comparison of the regulatory elements of the gh1 and gh2 genes reveals both shared and distinct features that underlie differences in their expression patterns and hormonal responsiveness. The gh paralogs possess conserved A/T-rich regions containing binding sites (F1–F4) for the transcription factor Pit‑1, also known as growth hormone factor 1 (GHF‑1 or POU1F1). The F1 site plays a key role in Pit‑1–mediated activation, whereas the F2–F4 sites enhance transcriptional activity (Bernardini et al., 1999; Argenton et al., 1996; Rhodes et al., 1996). This architecture supports expression of both genes in somatotrophs, as Pit‑1 is the principal determinant of pituitary‑specific growth hormone (GH) expression in vertebrates (Harvey et al., 2000), even though GH is also produced in multiple peripheral tissues where it functions as a local auto‑ or paracrine regulator (Harvey et al., 2012).

The gh2 paralog is characterized by a higher level of polymorphism, particularly within the F2 and F3 binding motifs. These variations suggest the presence of functional cis‑regulatory variants (cis‑eQTLs) that may alter transcriptional activity, tissue specificity, and hormonal sensitivity of the promoter. In contrast, the gh1 promoter remains highly conserved among species of the family Salmonidae, reflecting stabilizing selection maintaining precise Pit‑1–dependent expression in somatotrophs (Kamenskaya et al., 2017; Alberts et al., 2007).

The promoter regions of both genes contain hormone‑responsive regulatory elements with canonical motifs such as cAMP response elements (CRE), glucocorticoid response elements (GRE), and retinoic acid response elements (RAR/RXR). However, the gh2 promoter lacks an estrogen response element (ERE) present in gh1, which may reduce gh2 sensitivity to estrogen‑dependent signaling and represents a potential determinant of tissue‑specific expression differences (Yang et al., 1997). Furthermore, the CRE motif in gh2 differs from the palindromic sequence in gh1 by a single nucleotide substitution, potentially modifying the promoter’s responsiveness to cAMP‑mediated pathways (Kamenskaya et al., 2017).

An additional regulatory feature of gh2 is a long homopolymeric tract composed of 52 cytosines located within a fifth intronic region. The presence of such homopolymers can suppress gene expression, with polymer length inversely correlated with the level of transcriptional activity (Tesina et al., 2020). These regions can induce frameshift mutations or alter mRNA stability, increasing the energetic cost of transcription and manifesting as transcriptional attenuation (Kayhanian et al., 2024).

1.2. Pleiotropic effects of growth hormone and GH-IGF axis signaling pathways

Somatotropin exhibits pleiotropic effects, participating in a variety of physiological processes. Primarily, growth hormone regulates the synthesis and release of insulin-like growth factor, which mediates GH’s main anabolic effects on growth, particularly in skeletal muscle (Reid et al., 2024). In teleost fish, GH also plays crucial roles in reproductive development, osmoregulation, and immune response (Rousseau et al., 2004; Yada et al., 2005; Cohen-Rothschild et al., 2024). The regulatory factors controlling growth hormone gene expression differ even among ray-finned fish (Teleostei), such that the mechanisms of GH release and inhibition are distinct from those found in birds and higher vertebrates, including humans.

In vitro studies of GH gene expression in cultured pituitary cells of trout demonstrated GH secretion and gh gene expression in the absence of releasing hormones (Rousseau et al., 2004). Pituitary cells expressing GH genes possess high autonomous secretory activity but remain under dominant inhibitory control by the neurohormone somatostatin and IGF (Poppinga et al., 2007; Dai et al., 2015). It is plausible that the release of gh1 and gh2 genes in rainbow trout can occur independently of releasing hormones, supporting sustained growth throughout the fish’s lifespan. Furthermore, somatostatin neutralization enhances growth rate and feed conversion efficiency (Bazyar et al., 2016).

Different physiological states likely involve modulation of the GH gene by releasing hormones of the hypothalamic-pituitary axis. Growth hormone-releasing hormone (GHRH) stimulates growth; gonadotropin-releasing hormone (GnRH), together with the gonadotropic axis, initiates gametogenesis (Gomez et al., 1999b); dopamine (DA) is involved in stress responses (Ágústsson et al., 2000; Gesto et al., 2013); and the multifunctional neuropeptide PACAP, related to GHRH and produced in the nervous system and peripheral organs, activates pituitary adenylate cyclase (Rousseau et al., 2004; Dufour et al., 2020; Urban-Sosa et al., 2024). PACAP is, however, primarily recognized for its immunomodulatory role in teleosts (Velázquez et al., 2023; Saha et al., 2024).

The functional diversity of the GH gene is mediated through two receptor types encoded by ghr1 and ghr2, which differ in their binding affinities and the signaling cascades they activate (Brivanlou et al., 2002). Somatotropin phosphorylates and activates Janus kinase 2 (JAK2) via its receptors, initiating a signaling cascade involving phosphorylation of downstream effectors including ERK1/2, PI3K-Akt, and STAT5 pathways (Kittilson et al., 2011). In the liver of rainbow trout, GH stimulates the ERK and PI3K-Akt pathways, triggering molecular interactions that promote igf expression and regulate metabolic processes (Reindl et al., 2012).

These signaling mechanisms depend on the organism’s physiological state. For example, during fasting, GH predominantly activates ERK and PKC pathways, promoting lipolysis; whereas under normal feeding conditions, JAK/STAT and PI3K-Akt pathways dominate, supporting anabolism and growth (Bergan-Roller et al., 2018). Thus, the same hormone can modulate metabolic processes dynamically in response to the fish’s energetic status.

1.3. Expression profile of GH–IGF in embryonic development and ontogenesis of rainbow trout

The GH–IGF axis undergoes significant remodeling throughout the embryonic and ontogenetic development of rainbow trout, reflecting transitions from embryonic to juvenile and then to sexually mature stages (table 2). These changes are clearly traceable at the transcriptional level of key axis genes starting from early development stages.

During the incubation period, gh1 and gh2 mRNA levels remain low for the initial hours and the first three days of embryogenesis. Notably, similar gh paralog transcript levels are detected in unfertilized eggs, indicating maternal origin (Yang et al., 1999). The embryonic genome becomes transcriptionally active around days 2 to 5 post-fertilization, coinciding with somatotropic axis formation. At this stage, gh2 mRNA copy numbers slightly surpass those of gh1 (up to 1200 copies), suggesting a leading role for gh2 during early development (Gabillard et al., 2003). During organogenesis (days 8–27), gh gene signals are almost undetectable except on a few specific days when gh mRNA is likely synthesized de novo. gh gene expression sharply increases at larval hatching - day 31 (Yang et al., 1999), marking activation of the endogenous somatotropic system responsible for initiating post-embryonic growth, with gh products expressed abundantly in both the head and body of larvae (Yang et al., 1999). 

At stage of GH receptors and IGF system development both growth hormone receptor genes show similar mRNA levels during the last week of organogenesis and at hatching, although ghr1 expression is more sensitive to water temperature changes, while ghr2 expression remains stable regardless of temperature (Gabillard et al., 2006). Insulin-like growth factors genes experience a notable expression surge between days 5–7 post-fertilization, especially igf2 reaching up to 500 × 10³ mRNA copies, highlighting the critical role of IGFs in early organismal development (Gabillard et al., 2003; Li et al., 2007). This pattern suggests that gh paralogs initiate axis formation, while IGFs largely govern subsequent development.

In juveniles, gh mRNA is detected in both head and trunk tissues, indicating expansion of GH regulatory expression domains. The mRNA levels of igf1 and igf2 increase dramatically, reaching approximately 15 million and 9 million copies, respectively, which corresponds with the rapid growth of juveniles that have fully transitioned to exogenous feeding (Gabillard et al., 2003). In early-stage juveniles, following complete yolk sac absorption and the transition to external feeding, the mRNA levels of ghr1 and ghr2 in liver are approximately 100 copies. However, decreased temperature and restricted feeding trigger an upregulation in the expression of ghr-paralogs (Raine et al., 2007).

In one-year-old and mature rainbow trout, RT-PCR analyses reveal highest gh1 and gh2 expression in the pituitary and brain, moderate levels in gills and heart, and lower expression in kidney, liver, pyloric caeca, and gonads (Yang et al., 1999). Tissue-specific expression is also evident in ghr paralogs: juveniles exhibit higher ghr1 mRNA in the brain, whereas ghr2 is more abundant in the pancreas and spleen, implying independent regulatory mechanisms for these receptors (Very et al., 2005). In one-year-old rainbow trout, muscle growth stimulation and compensatory myogenesis following fasting and refeeding are primarily mediated by insulin-like growth factor 1 (Chauvigné et al., 2003).

During sexual maturation, systemic growth regulation shifts as reproductive organs mature and ovulation approaches. Gonadal steroids exert strong tissue-specific effects on the somatotropic axis. Estrogens inhibit ghr2 and igf gene expression in the liver but stimulate ghr2, igf1, and igf2 in muscle. Estrogen reduces IGF bioavailability by enhancing IGF binding protein (IGFBP) production, which suppresses anabolic signaling (Cleveland et al., 2015a; Cleveland et al., 2015b). This effect coincides with increased vitellogenin synthesis, a yolk protein precursor marker reflecting liver metabolic reprogramming for oocyte development (Gupta et al., 2021). Conversely, another group of sex hormones, the androgens, stimulate somatotropic axis activity in the liver, which supports growth, but reduce igf2 and igfbp5b1 expression in muscle (Cleveland et al., 2015a; Vélez et al., 2017). Thereby, maintaining high nutritional status during maturation is crucial to counteract muscle wasting resulting from skeletal muscle atrophy driven by lowered ghr and igf expression and resource reallocation toward vitellogenin production necessary for reproduction (Nemova et al., 2021; Weber et al., 2022).

In rainbow trout females, somatotropin, predominantly GH2 - is key during oocyte growth, vitellogenesis, and final follicle maturation (Li et al., 2007), while IGF has no direct effect on oogenesis or overall oocyte growth (Weber, 2023). In males, GH concentrations decrease in testes from spermatogonial proliferation through the completion of spermatogenesis (Gomez et al., 1998). GH and IGF-I strongly modulate spermatogonial proliferation (Loir, 1999); however, as spermatogenesis progresses to later stages, GH’s role shifts from cellular proliferation stimulation to other functions, reflected by reduced GH levels in testicular tissue.

Table 2. - Expression profile of GH-IGF components during embryonic development and ontogeny of rainbow trout based on literature of current chapter. In their studies on gene expression levels during embryogenesis, the authors followed the chronological sequence of embryonic and larval development stages of trout as described by Vernier in 1969 (Vernier J.M. 1969. Table chronologique du développement embryonnaire de la truite arc en ciel, Salmo Gairdneri. An Emb Morpho 2:495–520), which are also synchronized with the stages used in the present study, as shown in this table. The days are approximate, as they may vary depending on various factors. The larval stage 30-37 is not included, and milestones in fish life after hatching are outlined concisely.

From endogenous control to exogenous determinants

As previously noted, the functioning of the somatotropic axis and its associated metabolic processes are contingent on the current physiological state of rainbow trout. The activity and interplay of the GH-IGF axis components are significantly influenced by factors such as lighting conditions, water temperature, smoltification stage, social hierarchy, and specific aquaculture rearing practices. Since these factors delineate the context within which the regulatory mechanisms of the hormonal system operate, their roles will be examined in detail in the following chapter.

2. Physiological and environmental determinants of somatotropic axis function

2.1. Circadian Rhythms

Photoperiod is a significant environmental factor in the rearing of rainbow trout as it shapes circadian patterns of genes and hormones associated with the GH-IGF axis (Dong et al., 2024). In salmonids, an extended photoperiod enhances growth by increasing food consumption and stimulating somatic growth in the pre-spawning and post-spawning periods, as well as improving resistance to fungal diseases. (Lundová et al., 2019). Rearing pre-spawning rainbow trout under continuous light with nocturnal feeding increases specific growth rate, driven by stimulation of GH axis components (ghr1, ghr2, igf1, igf2, igfr1a, igfbp2a) and sustained high expression of myogenic regulatory factors (myod, myf5, mstn1a) as well as myosin heavy and light chains (myhc, mlc2), likely reflecting enhanced aerobic metabolism (Rodin et al., 2025; Kuznetsova et al., 2025).

In juvenile rainbow trout, efficient growth and feed utilization are not directly determined by photoperiod length, but are markedly improved by daytime feeding at fixed times. Such scheduled feeding entrains feeding activity and associated biochemical processes, including digestive enzyme activity and circulating levels of glucose, triglycerides, and hormones (Xu et al., 2022). By contrast, continuous lighting during juvenile rearing can induce immunosuppression and increase energetic costs. This stress is manifested as reduced lysozyme secretion and elevated mucin concentration in skin mucus, along with alterations in leukocyte profiles, particularly in monocytes and macrophages, which act in concert with lysozymes in non-specific defense (Valenzuela et al., 2022).

Prolonged photoperiods therefore appear more suitable for rainbow trout that have reached reproductive age when the production target is carcass yield rather than roe, because extended light promotes somatic growth while suppressing gonadal development and delaying the timing of reproductive activity (Noori et al., 2015; Mennigen et al., 2022; Al-Emran et al., 2024). This may be linked to differential regulation of growth hormone paralogs, as gh2 activity increases during the dark phase in contrast to gh1 and is generally higher in females approaching sexual maturity (Li et al., 2007; Dong et al., 2024). Growth hormone, particularly GH2, is potentially important during the initiation of oocyte growth, vitellogenesis, and final follicular maturation (Gómez et al., 1999a) (fig. 2).

Figure 2. Schematic representation of the effect of modulated circadian rhythms across the somatotropic axis on growth, immunity, and reproduction in rainbow trout.

2.2. Osmoregulation

Smoltification in Salmonidae species naturally begins in spring in response to increasing daylight. As a euryhaline species, rainbow trout adapts to fluctuating salinity through an energy trade-off within the GH–IGF axis balancing growth and osmoregulation (Xiang et al., 2022). Osmoregulatory processes enhance GH secretion (Sakamoto et al., 1993), which supports improved growth rates during transfer from freshwater to seawater in aquaculture (Kaneko et al., 2019).

Smoltification precedes a phase of rapid post-smolt growth, initiating earlier transcription of igf-1, ghr, insulin receptor igfbp1b, and ctsl genes, the latter encoding a protein essential for intracellular protein catabolism. Completion of smoltification is marked by accelerated growth, increased gill Na+/K+-ATPase activity, and elevated plasma growth hormone levels (Morro et al., 2019; Shulgina et al., 2021). Recent omics studies reveal that both endocrine factors and gut microbiota contribute to salinity adaptation regulation (Mkulo et al., 2025).

Salinity levels from minimal to threshold values differently influence transcription of GH–IGF axis components. Expression of gh increases with salinity rising from 0 to 24‰ but markedly decreases near the threshold of 32‰, possibly reflecting resource depletion or reallocation for survival (Bi et al., 2021). This aligns with findings of increased plasma GH during stepwise acclimation to tolerated salinities (Shulgina and Mkulo). While igf1 gene expression remains steady at threshold salinity, IGF-binding proteins expression significantly declines, potentially leading to pathological liver changes (Bi et al., 2021; Cui et al., 2022).

In gills, ghr1 and ghr2 transcript levels differ little between parr and smolts, indicating that growth hormone receptors may not critically influence salinity acclimation during the parr-to-smolt transformation (Kusakabe et al., 2025).

Thus, during transfer to seawater, growth hormone prioritizes osmoregulation by suppressing growth temporarily. Upon stabilization of internal osmotic conditions at relatively constant levels, fish exhibit rapid growth spurts, signaling successful acclimation and positive salinity effects on growth and health (fig. 3).

Figure. 3. Dynamic equilibrium of the GH-IGF axis during rainbow trout adaptation to salt water. Schematic diagram of growth activity and osmoregulation during the main stages of rainbow trout transition from fresh water to salt water. During smoltification and the initial transition to seawater, osmoregulatory processes dominated, supported by increased growth hormone secretion and increased activity of Na+/K+-ATPase in the gills, while growth was temporarily suppressed (Morro et al., 2019; Shulgina et al., 2021). The expression of genes involved in the GH-IGF axis depends on the salinity stage: gh transcripts typically increase with increasing salinity, while IGF-binding proteins decrease, indicating a redistribution of energy towards osmoregulation (Bi et al., 2021; Xiang et al., 2022). After successful osmoregulatory adaptation, insulin-like growth factor-induced growth resumes, leading to enhanced somatic development in the post-smolt stage (Kaneko et al., 2019).

2.3. Social behaviour: hierarchy, aggression. Influence on sexual dimorphism.

The somatotropic axis also plays an important role in shaping social hierarchy in juvenile rainbow trout. Although gh1 and gh2 pituitary expression does not differ between dominant and subordinate fish, subordinates exhibit higher circulating GH concentrations. In dominant individuals, expression of ghr and igf paralogs is elevated, supporting anabolic processes and promoting growth, whereas subordinates show increased expression of igfbp paralogs, which limit IGF signaling and shift metabolism toward catabolism and lipolysis (Mennigen et al., 2022; Best et al., 2023). Thus, the GH–IGF axis acts as a mediator of social status–dependent differences in energy metabolism and growth.

Enhanced GH action influences social interactions by increasing aggression, including territorial behavior (Jönsson et al., 1998). Expression of the growth hormone gene is continuously restrained by negative feedback from IGF1 and somatostatin (SST) (Rousseau et al., 2004; Canosa et al., 2007). This feedback may represent a selective pressure against chronically high GH levels that would otherwise drive excessive aggression, elevated energy expenditure, and increased mortality (Jönsson et al., 1998).

Growth hormone genes also contribute to sexual dimorphism alongside key Y‑linked loci such as dmrt1, amh, gsdf, foxl2, and cyp19a1a, which govern sex-linked traits and direct male-type development under the chromosomal sex-determination system of rainbow trout (Li et al., 2022). Males and females differ anatomically in the geometric configuration of body and head landmarks, and males display pronounced nuptial coloration and secondary sexual traits during spawning to attract females and compete with rivals (Auld et al., 2019; Turgut et al., 2024). These morphometric traits are associated with regulatory elements in intronic regions of the gh gene, particularly nucleotide repeats that can alter expression patterns (Zhang et al., 2025).

On the Y chromosome of male rainbow trout, a gh pseudogene (gh-ψ) is located near variation in intron 5 of gh2 and its flanking regions. This putative pseudogene has been incorporated into PCR-based test systems for early sex determination and detection of neo-females in breeding programs (Akbarialmajough et al., 2020).

2.4. Temperature regime

A distinctive feature of fish biology is their capacity for continuous growth throughout life. Growth can be constrained by various physical factors, among which water temperature is one of the most influential. Although rainbow trout is traditionally regarded as a cold-water aquaculture species (Singh et al., 2024), some populations inhabit environments well beyond the typical range of other salmonids and occur in tropical and subequatorial climatic zones (Nevoux et al., 2022). Temperature regimes differentially affect expression of somatotropic axis genes during rainbow trout embryo and post-embryonic development, with direct consequences for growth.

During early development, increased temperature has little apparent effect on GH levels but strongly modulates expression of igf2, the somatotropic axis gene with the highest embryonic expression. Depending on the incubation stage (days 22, 24, 25, and hatching), igf2 mRNA levels can either increase or decrease, although they remain relatively high overall (Gabillard et al., 2005). Even modest elevation of incubation temperature (from 6°C to 8.5°C) causes a marked reduction in igf2 mRNA in embryos (Li et al., 2008).

Later in ontogeny, rainbow trout growth rate becomes proportional to plasma GH concentration. Elevated temperatures within the species’ tolerated range (14–18°C) increase plasma GH and promote growth (Kocmarek et al., 2014), whereas at lower temperatures (around 8°C) GH levels constrain growth rate (Gabillard et al., 2003). When water temperature exceeds 20°C, fish develop hyperthermia, gh gene expression declines, and growth is suppressed (Kocmarek et al., 2014). Nevertheless, some rainbow trout populations can persist at much higher temperatures. In Turkey, for example, seasonal surface water temperatures may range from 18°C in mid-winter to 27°C in mid-summer, and expression levels of GH–IGF axis components vary in both juveniles and mature cultured trout across seasons. In adults, temperature-dependent regulation of igf1 expression appears essential to maintain tissue metabolism and physiological plasticity. igf1 mRNA levels in muscle are substantially higher in mature fish, whereas in juveniles hepatic igf1 and igf2 expression is consistently slightly higher than in adults regardless of season (Tekeli et al., 2023), likely reflecting a more prominent role of liver-derived IGFs in systemic growth and development at early ontogenetic stages (Păpuc et al., 2025).

2.5. Unfavourable conditions for aquaculture

Adverse rearing conditions exert a pronounced influence on the functioning of GH–IGF axis components in rainbow trout. High stocking density induces stress through competition for oxygen, feed, and space, which alters igf1 expression and affects the biochemical status of the fish (Zahedi et al., 2017; Naderi et al., 2017). Prolonged crowding activates cellular homeostatic pathways such as autophagy, mitophagy, and ubiquitin–proteasome-mediated protein degradation, while suppressing spliceosome function, nucleo-cytoplasmic transport, and mRNA surveillance. This response reduces igf1 expression and promotes degradation of skeletal muscle proteins (Valenzuela et al., 2020; Aravena-Canales et al., 2025).

Chronic stress is accompanied by sustained elevation of cortisol, a potent anorexigenic factor in rainbow trout (Conde-Sieira et al., 2018). Although the promoters of gh paralogs contain glucocorticoid-responsive elements and chronic cortisol elevation upregulates gh1 and gh2 transcription, circulating GH levels remain low due to changes in GH synthesis, secretion, and metabolism (Kamenskaya et al., 2020). In parallel, hepatic expression of insulin-like growth factor binding protein 1 (igfbp1) increases persistently, and this factor acts as a growth repressor by attenuating igf1 signaling and redirecting energy reserves within the GH–IGF axis (Madison et al., 2015).

Under acute stress, cortisol transiently stimulates GH synthesis and secretion, leading to elevated plasma GH concentrations (Faught et al., 2016). However, short-term cortisol exposure downregulates ghr paralogs and igf1 expression in the liver, inducing a state of GH resistance in which tissues become less responsive to GH despite its high circulating levels (Canosa et al., 2023).

In summary, acute cortisol exposure (short-term stress) is associated with elevated plasma GH, whereas chronic cortisol elevation (long-term stress) drives increased pituitary gh transcription but simultaneously enhances inhibitory mechanisms that lower circulating GH and suppress growth.

The practice of fasting is another significant source of stress for aquaculture, with major consequences. It triggers endocrine reprogramming, stress hormone synthesis, and marked shifts in the physiological state of rainbow trout. It alters the activity of the GH–IGF axis and downstream metabolic pathways, with clear consequences for growth performance and muscle condition (Polaz et al., 2022). In vitro experiments on rainbow trout myogenic precursor cell cultures show that under “fasting” conditions (serum deprivation), GH no longer stimulates expression of key genes driving proliferation (myod1, myf5, pcna), differentiation and growth (igf1, igf2, myog, pax7a1, pax7a2). Instead, expression of genes promoting growth inhibition and proteolysis (atg4b, gabarapl1, lc3b, fbxo32) increases, indicating activation of autophagy and protein degradation pathways. Even so, GH can partially offset fasting-induced damage by upregulating ghr1 transcription in myotubes, helping to maintain some GH sensitivity (Reid et al., 2024). In vivo fasting studies in rainbow trout demonstrate that food deprivation activates ERK and PKC signaling and enhances lipid catabolism against a background of reduced growth. Under these conditions, GH fails to activate PI3K/Akt and JAK/STAT pathways in primary hepatocytes isolated from fasted fish. Instead, GH stimulates expression and activation of hormone-sensitive lipases HSL1 and HSL2, promoting mobilization of hepatic triglyceride stores via PLC- and ERK-dependent signaling (Bergan et al., 2012). Stress is further exacerbated when fish are fed at random times rather than on a fixed schedule, as unpredictable feeding increases physiological stress load (Xu et al., 2022). During prolonged fasting, the GH–IGF system is reshaped by leptin, a key regulator of energy metabolism, alongside suppression of genes involved in lipid metabolism and gluconeogenesis. Expression of ghr1 decreases in liver, adipose tissue, and both red and white muscle (Walock et al., 2014). Leptin elevates circulating GH but simultaneously blunts its effect on igf1 expression, inducing GH resistance under catabolic conditions. This adjustment conserves metabolic energy by downregulating enzymes of lipid and carbohydrate metabolism and inevitably slows growth (Gong et al., 2022).

Normalizing feeding, by contrast, reactivates JAK/STAT and PI3K/Akt signaling, restoring intracellular pathways that favor anabolism and growth in rainbow trout tissues (Bergan et al., 2012). Under chronic stress, GH signaling through JAK/STAT5 in the liver is impaired because these pathways induce suppressors of cytokine signaling (socs1, socs2), which mediate the glucocorticoid response to elevated cortisol. This results in reduced growth rates and impaired immune function (Philip et al., 2015). Cortisol-driven modulation of socs gene expression under chronic stress therefore contributes to both growth suppression and immunodepression.

Overall, adverse influences on rainbow trout particularly fasting and chronic stress elicit coordinated molecular responses within the somatotropic axis. Although the specific pathways activated may differ, the phenotypic outcome remains consistent: reduced growth and visible growth retardation in affected fish.

Conclusion

A review of the available literature indicates that duplication of somatotropic axis genes in rainbow trout has led to functional divergence of their paralogs while preserving an overall common regulatory framework. The gh1 and gh2 genes are highly conserved in structure, particularly across exons 2–5, consistent with retention of shared core hormonal functions. At the same time, differences in the length of exon 1 and intronic regions, together with unique regulatory elements in gh2, point to its adaptation to more specialized physiological roles. For example, gh2 shows elevated activity in female reproductive tissues and contributes more strongly to the regulation of vitellogenesis, whereas gh1 maintains a primary role in supporting somatic growth and basal pituitary GH secretion.

A similar pattern of functional complementarity is evident in other genes of the somatotropic axis. The paralogous receptors ghr1 and ghr2 encode proteins with distinct affinities and tissue distributions: ghr1 is predominantly expressed in liver and brain, mediating systemic GH actions, while ghr2 is more active in peripheral and digestive organs, suggesting a greater involvement in metabolic regulation and immune-related functions. An analogous division of labor is observed for insulin-like growth factors, where igf2 is crucial during early embryogenesis, driving cell proliferation and differentiation, and igf1 becomes the principal mediator of GH-dependent anabolic effects in later ontogeny and adulthood. As a result, dominance shifts between paralogs according to developmental stage, physiological status, and environmental influences such as temperature, photoperiod, salinity, and stress.

Overall, the functional diversity of rainbow trout somatotropic paralogs arises from the combination of strong structural conservation and adaptive modulation of gene expression. The paralogs described in this review do not merely duplicate functions but partition and specialize them, providing fine-tuned regulation of growth, metabolism, reproduction, and environmental adaptation. This organization of the somatotropic axis confers high phenotypic plasticity and resilience to environmental fluctuations in rainbow trout, with important implications for improving aquaculture performance and the design of selective breeding programs.

Funding

This work was supported by the Ministry of Science and Higher Education of the Russian Federation (project FGGN-2024-0015).

References

1. Agellon L. B., Davies S. L., Lin C. M., Chen T. T., Powers D. A. Rainbow trout has two genes for growth hormone // Molecular reproduction and development. – 1988. –1. – №.1. – P.11–17. doi:10.1002/mrd.1080010104
2. Ágústsson T., Ebbesson L. O., Björnsson B. T. 2000. Dopaminergic innervation of the rainbow trout pituitary and stimulatory effect of dopamine on growth hormone secretion in vitro // Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology. – – V. 127. – №3. – P.355–364. doi:10.1016/S1095–6433(00)00265–8
3. Akbarialmajough T., Manaffar R., Najdegerami E. H., Bossier P. New insight into the diversity of exon and intron 5 regions of Oncorhynchus mykiss growth hormone (GH) gene: sexual dimorphism in the GH gene // Reviews in Aquaculture. – – V.12. – №1. – P. 254–260. doi:10.1111/raq.12315
4. Alberts R., Terpstra P., Li Y., Breitling R., Nap J. P., Jansen R. C. Sequence polymorphisms cause many false cis eQTLs. PloS one. – 2007. – V.2(7). – e622. doi:10.1371/journal.pone.0000622
5. Al-Emran M., Zahangir M.M., Badruzzaman M., Shahjahan M. Influences of photoperiod on growth and reproduction of farmed fishes-prospects in aquaculture // Aquaculture Reports. – – V.35. – 101978. doi:10.1016/j.aqrep.2024.101978
6. Altschul S. F., Madden T. L., Schäffer A. A., Zhang J., Zhang Z., Miller W., Lipman, D. J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs // Nucleic Acids Research. – – V.25. – №.17. – P.3389–3402. doi:10.1093/nar/25.17.3389
7. Aravena-Canales D., Valenzuela-Muñoz V., Gallardo-Escarate C., Molina A., Valdés J. A. Molecular and epigenetic responses to crowding stress in rainbow trout (Oncorhynchus mykiss) skeletal muscle // Frontiers in Endocrinology. – –№16. – 1571111. doi:10.3389/fendo.2025.1571111
8. Argenton F., Bernardini S., Puttini S., Colombo L., Bortolussi M.A TGACG Motif Mediates Growth‐Hormone‐Factor‐1/Pituitary‐Transcriptional‐Activator‐1‐Dependent cAMP Regulation of the Rainbow Trout Growth‐Hormone Promoter// European journal of biochemistry. – 1996. –238 – №3. – P.591–598. doi:10.1111/j.1432-1033.1996.0591w.x
9. Auld H.L., Noakes D. L., Banks M.A. 2019. Advancing mate choice studies in salmonids // Reviews in Fish Biology and Fisheries. – – V.29. – №2. – P.249–276. doi:10.1007/s11160–019–09551–5
10. Bazyar Lakeh A. A., Farahmand H., Kloas W., Mirvaghefi A., Trubiroha A., Peterson B. C., Wuertz, S. Growth enhancement of rainbow trout (Oncorhynchus mykiss) by passive immunization against somatostatin-14 // Aquaculture International. – – V.24. – №1. – P.11–21. doi:10.1007/s10499–015–9905–8
11. Bergan H.E., Kittilson J.D., Sheridan M.A. Nutrition-regulated lipolysis in rainbow trout (Oncorhynchus mykiss) is associated with alterations in the ERK, PI3K-Akt, JAK-STAT, and PKC signaling pathways // General and comparative endocrinology. – – V.176. – №3. – P.367–376. doi:10.1016/j.ygcen.2011.12.013
12. Bergan-Roller H.E., Sheridan M.A. The growth hormone signaling system: Insights into coordinating the anabolic and catabolic actions of growth hormone // General and comparative endocrinology. – – V.258. – P.119–133. doi:10.1016/j.ygcen.2017.07.028
13. Bernardini S., Argenton F., Vianello S., Colombo L., Bortolussi, M. Regulatory regions in the promoter and third intron of the growth hormone gene in rainbow trout, Oncorhynchus mykiss Walbaum // General and comparative endocrinology. – 1999. – 116. – №2. – P.261–271. doi:10.1006/gcen.1999.7367
14. Best C., Jennings K., Culbert B. M., Flear K., Volkoff H., Gilmour K. M. Too stressed to eat: investigating factors associated with appetite loss in subordinate rainbow trout // Molecular and Cellular Endocrinology. – –V.559. – 111798. doi:10.1016/j.mce.2022.111798
15. Bi B., GaoY., Jia D., Kong L., Su Y., Rong H., Wu X., Wang X., Hu Z., Hu Q.. Growth influence of juvenile golden trout (Oncorhynchus mykiss) in different osmotic conditions: implications for tissue histology, biochemical indicators, and genes transcription involved in GH/IGF system // Fish physiology and biochemistry. – – V.47. – №2. – P.583–597. doi:10.1007/s10695–021–00933–w
16. Blay C., Haffray P., Bugeon J., D'Ambrosio J., Dechamp N., Collewet G., et al. Genetic Parameters and Genome-Wide Association Studies of Quality Traits Characterised Using Imaging Technologies in Rainbow Trout, Oncorhynchus mykiss // Frontiers in genetics. – – V.12. – 639223. doi:10.3389/fgene.2021.639223
17. Brivanlou A.H., Darnell J.E.J. Signal transduction and the control of gene expression // Science. – – V.295. – №5556. – P.813–818. doi:10.1126/science.1066355
18. Canosa L. F., Bertucci J. I. The effect of environmental stressors on growth in fish and its endocrine control // Frontiers in endocrinology. – – V.14. – 1109461. doi:10.3389/fendo.2023.1109461
19. Canosa L.F., Bertucci J.I. Nutrient regulation of somatic growth in teleost fish. The interaction between somatic growth, feeding and metabolism // Molecular and Cellular Endocrinology. – – V.518. –111029. doi:10.1016/j.mce.2020.111029
20. Canosa L.F., Chang J.P., Peter R.E. Neuroendocrine control of growth hormone in fish // General and Comparative Endocrinology. – – V.151. – №1. – P.1–26. doi:10.1016/j.ygcen.2006.12.010
21. Chandhini S., Trumboo B., Jose S., Varghese T., Rajesh M., Kumar V.J.R. Insulin-like growth factor signaling and its significance as a biomarker in fish and shellfish research // Fish physiology and biochemistry. – – V.47. – № 4. –P.1011–1031. doi:10.1007/s10695–021–00961–6
22. Chauvigné F., Gabillard J.C., Weil C., Rescan P.Y. Effect of refeeding on IGFI, IGFII, IGF receptors, FGF2, FGF6, and myostatin mRNA expression in rainbow trout myotomal muscle // General and comparative endocrinology. – 2003. V.132(2). – P.209-215. doi:10.1016/S0016-6480(03)00081-9
23. Chen T. T., Marsh A., Shamblott M., Chan K. M., Tang Y. L., Cheng C. M., Yang B. Y. 6 structure and evolution of fish growth hormone and insulin like growth factor genes // Fish physiology. – –V.13. – P.179–209. doi:10.1016/S1546–5098(08)60067–9
24. Cleveland B. M., Yamaguchi G., Radler L. M., Shimizu M. Editing the duplicated insulin-like growth factor binding protein-2b gene in rainbow trout (Oncorhynchus mykiss) // Scientific reports. – – V.8. – №1. – P.16054–16067. doi:10.1038/s41598–018–34326–6
25. Cleveland B.M., Manor M.L. Effects of phytoestrogens on growth-related and lipogenic genes in rainbow trout (Oncorhynchus mykiss) // Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology. – –V.170. – P.28-37. doi:10.1016/j.cbpc.2015.02.001
26. Cleveland B.M., Weber, G.M. Effects of sex steroids on expression of genes regulating growth-related mechanisms in rainbow trout (Oncorhynchus mykiss) // General and comparative endocrinology. – – V.216. – P.103-115. doi:10.1016/j.ygcen.2014.11.018
27. Cohen-Rothschild N., Mizrahi N., Levavi-Sivan B. Characterization of a novel fast-growing zebrafish: a new approach to growth hormone transgenesis // Frontiers in Endocrinology. – – V.15. – 1369043. doi:10.3389/fendo.2024.1369043
28. Cui W., Takahashi E., Morro B., Balseiro P., Albalat A., Pedrosa C., et al. Changes in circulating insulin-like growth factor-1 and its binding proteins in yearling rainbow trout during spring under natural and manipulated photoperiods and their relationships with gill Na⁺, K⁺-ATPase and body size // Comparative biochemistry and physiology. Part A, Molecular & integrative physiology. – – V.268. – 111205. doi:10.1016/j.cbpa.2022.111205.
29. Dai X., Zhang W., Zhuo Z., He J., Yin Z. Neuroendocrine regulation of somatic growth in fishes. Science. China Life Science. – – V.58. – P.137–147. doi:10.1007/s11427–015–4805–8
30. Dong K, Hou Z, Li Z, Xu Y, Gao Q. Extended Photoperiod Facilitated the Restoration of the Expression of GH-IGF Axis Genes in Submerged Rainbow Trout (Oncorhynchus mykiss) // International Journal of Molecular Sciences. – – V.25. – №24. – P.13583–13600. doi:10.3390/ijms252413583
31. Dufour S., Rousseau K. 2020. Endocrinology: An Evolutionary Perspective on Neuroendocrine Axes in Teleosts // In The Physiology of Fishes (5^th Edition). Chennai:CRC Press. P. 105– doi:10.1201/9781003036401
32. Dysin A.P., Shcherbakov Y.S., Nikolaeva O.A. Terletskii V.P., Tyshchenko V.I., Dementieva N.V. Salmonidae genome: features, evolutionary and phylogenetic characteristics // – 2022. – V.13. – №12. – 2221. doi:10.3390/genes13122221
33. Faught E., Vijayan M. M. Mechanisms of cortisol action in fish hepatocytes // Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology. – – V.199. – P.136–145. doi:10.1016/j.cbpb.2016.06.012
34. Food and Agriculture Organization. FAO yearbook:  Fishery and Aquaculture Statistics: J - Software for Fishery and Aquaculture Statistical Time Series (FAO, 2024)
35. Gabillard J.C., Rescan P.Y., Fauconneau B., Weil C., Le Bail P.Y. Effect of temperature on gene expression of the Gh/Igf system during embryonic development in rainbow trout (Oncorhynchus mykiss) // Journal of Experimental Zoology Part A: Comparative Experimental Biology. – – V.298. – №2. – P.134–142. doi:10.1002/jez.a.10280
36. Gabillard J.C., Weil C., Rescan P. Y., Navarro I., Gutiérrez J., Le Bail P. Y. Does the GH/IGF system mediate the effect of water temperature on fish growth? A review // Cybium. – – V.29. – №2. – P.107–117. doi:10.26028/cybium/2005–292–001
37. Gabillard J.C., Yao K., Vandeputte M., Gutierrez J., Le Bail P.Y. Differential expression of two GH receptor mRNAs following temperature change in rainbow trout (Oncorhynchus mykiss) // Journal of Endocrinology. – –V.190. – №1. – P.29–37. doi:10.1677/joe.1.06695
38. Gesto M., López-Patiño M. A., Hernández J., Soengas J. L., Míguez J. M. The response of brain serotonergic and dopaminergic systems to an acute stressor in rainbow trout: a time course study // Journal of Experimental Biology. – –V.216. – №23. – P.4435–4442. doi:10.1242/jeb.091751
39. Gabillard J.C., Weil C., Rescan P.Y., Navarro I., Gutiérrez J., Le Bail P.Y. Effects of environmental temperature on IGF1, IGF2, and IGF type I receptor expression in rainbow trout (Oncorhynchus mykiss) // General and Comparative Endocrinology. – 2003. – V.133(2). – P.233-242. doi:10.1016/S0016-6480(03)00167-9
40. Gomez J. M., Weil C., Ollitrault M., Le Bail P. Y., Breton B., Le Gac F. Growth hormone (GH) and gonadotropin subunit gene expression and pituitary and plasma changes during spermatogenesis and oogenesis in rainbow trout (Oncorhynchus mykiss) // General and comparative endocrinology. – –V.113 – №3. – P.413–428. doi:10.1006/gcen.1998.7222
41. Gomez J.M., Loir M., Gac F.L. Growth hormone receptors in testis and liver during the spermatogenetic cycle in rainbow trout (Oncorhynchus mykiss). Biology of reproduction. – – V.58. – №2. – P.483–491. doi:10.1095/biolreprod58.2.483
42. Gomez J.M., Mourot B., Fostier A., Le Gac F. Growth hormone receptors in ovary and liver during gametogenesis in female rainbow trout (Oncorhynchus mykiss) // Reproduction. – – V.115. – №2. – P.275-285. doi:10.1530/jrf.0.1150275
43. Gong N., Lundin J., Morgenroth D., Sheridan M.A., Sandblom E., Björnsson B.T. Roles of leptin in initiation of acquired growth hormone resistance and control of metabolism in rainbow trout // American journal of physiology. Regulatory, integrative and comparative physiology. – – V.322 – №5. –R434–R444. doi:10.1152/ajpregu.00254.2021
44. Gupta G., Kumar M., Rani S., Mohanta B. 2021. Vitellogenesis and Their Endocrine Control in Fishes // Recent updates in molecular Endocrinology and Reproductive Physiology of Fish. Singapore: Springer. P.23– doi:10.1007/978–981–15–8369–8_2
45. Harvey S., Arámburo C., Sanders E.J. Extrapituitary production of anterior pituitary hormones: an overview // Endocrine. – 2012. – V. – P.19–30. doi:10.1007/s12020-011-9557-z
46. Harvey S., Azumaya Y., Hull K.L. Pituitary and extrapituitary growth hormone: Pit-1 dependence? // Canadian journal of physiology and pharmacology. 2000. –V.78(12). – P.1013–1028. doi:10.1139/y00-095
47. Hayashida T., Farmer S.W., Papkoff H. Pituitary growth hormones: further evidence for evolutionary conservatism based on immunochemical studies // Proceedings of the National Academy of Sciences. – – V.72. – №11. –P.4322–4326. doi:10.1073/pnas.72.11.4322
48. Hu Y., Wang X., Xu Y., Yang H., Tong Z., Tian R., et al. Molecular mechanisms of adaptive evolution in wild animals and plants. Science China Life Science. – – V.66. – P.453–495. doi:10.1007/s11427–022–2233–x
49. Izutsu A., Tadokoro D., Habara S., Ugachi Y., Shimizu M. Evaluation of circulating insulin-like growth factor (IGF)-I and IGF-binding proteins as growth indices in rainbow trout (Oncorhynchus mykiss) // General and Comparative Endocrinology. – –V.320. – 114008. doi:10.1016/j.ygcen.2022.114008
50. Jönsson E., Johnsson J.I., Björnsson B.T. Growth hormone increases aggressive behavior in juvenile rainbow trout // Hormones and Behavior. – –V.33. – №1. – P.9–15. doi:10.1006/hbeh.1997.1426
51. Kamenskaya D.N., Brykov V.A. Fish Growth Hormone Genes: Structure and Divergence // Russian Journal of Marine Biology. – – V.46. – №4. – P.219–230. (In Russ.). doi:10.31857/S0134347520040038
52. Kamenskaya D.N., Pankova M.V., Atopkin D.M., Brykov V.A. Divergence of Paralogous Growth Hormone Encoding Genes and Their Promoters in Salmonidae // Molecular biology. – – V.51, №2. P.314–323. (In Russ.). doi:10.7868/S0026898417020124
53. Kamenskaya D.N., Pankova M.V., Atopkin D.M., Brykov V.A. Fish growth hormone genes: functionality evidence of paralogous genes in Levanidov`s charr Salvelinus levanidovi // Molecular biology. – – V.49. – №5. – P.770–770. (In Russ.). doi:10.7868/S0026898415050092
54. Kaneko T., Suzuki R., Watanabe S., Miyanishi H., Matsuzawa S., Furihata M., Ishida N. Past seawater experience enhances subsequent growth and seawater acclimability in a later life stage in rainbow trout Oncorhynchus mykiss // Fish Science. – – V.85. – P.925–930. doi:10.1007/s12562–019–01351–x
55. Kayhanian H., Cross W., van der Horst S.E.M., Barmpoutis P., Lakatos E., Caravagna G., et al. Homopolymer switches mediate adaptive mutability in mismatch repair-deficient colorectal cancer // Nature Genetics. – – V.56. – №7. – P.1420–1433. doi:10.1038/s41588–024–01777–9
56. Kittilson J.D., Jones E., Sheridan M.A. ERK, Akt, and STAT5 are differentially activated by the two growth hormone receptor subtypes of a teleost fish (Oncorhynchus mykiss) // Frontiers in Endocrinology. – – V.2. – №30. – P.1–7. doi:10.3389/fendo.2011.00030
57. Kocmarek, A.L., Ferguson, M.M., Danzmann, R.G. Differential gene expression in small and large rainbow trout derived from two seasonal spawning groups. BMC Genomics. – – V.15. – №5. – P.57–76. doi:10.1186/1471–2164–15–57
58. Kusakabe M., Yada T., Young G., Regish A.M., McCormick S.D. Expression of corticoid‐regulatory genes in the gills of Atlantic salmon (Salmo salar) parr and smolt and during salinity acclimation // Journal of Fish Biology. – – 10.1111/jfb.70119. doi:10.1111/jfb.70119
59. Kuznetsova, M. V., Rodin, M. A., Shulgina, N. S., Krupnova, M. Y., Kuritsyn, A. E., Nemova, N. N. Gene Expression of GH/IGF Axis Components and Myogenic Regulatory Factors in Juvenile Rainbow Trout (Oncorhynchus mykiss Walb.) under the Influence of Continuous Lighting // Journal of Evolutionary Biochemistry and Physiology. – – V.61. – №1. – P.162–176. doi:10.1134/S0022093025010132
60. Li M., Gao Z., Ji D., Zhang S. Functional characterization of GH-like homolog in amphioxus reveals an ancient origin of GH/GH receptor system // Endocrinology. – – V.155. – №12. – P.4818–4830. doi:10.1210/en.2014–1377
61. Li M., Leatherland, J. Temperature and ration effects on components of the IGF system and growth performance of rainbow trout (Oncorhynchus mykiss) during the transition from late stage embryos to early stage juveniles // General and Comparative Endocrinology. – – V.155. – №3. – P.668–679. doi:10.1016/j.ygcen.2007.08.017
62. Li M., Raine J.C., Leatherland J.F. Expression profiles of growth-related genes during the very early development of rainbow trout embryos reared at two incubation temperatures // General and comparative endocrinology. – –V.153. – №1–3. – P.302–310. doi:10.1016/j.ygcen.2007.02.012
63. Li X.Y., Mei J., Ge C.T., Liu X.L., Gui J.F. Sex determination mechanisms and sex control approaches in aquaculture animals // Science China Life Sciences. – – V.65. – №6. – P.1091–1122. doi:10.1007/s11427–021–2075–x
64. Loir M. Spermatogonia of rainbow trout: II. in vitro study of the influence of pituitary hormones, growth factors and steroids on mitotic activity // Molecular Reproduction and Development: Incorporating Gamete Research. – – V.53. – №4. – P.434–442. doi:10.1002/(SICI)1098–2795(199908)53:4<434::AID–MRD9>3.0.CO;2–L
65. Lundova K., Matousek J., Prokesova M., Vanina T., Sebesta R., Urban J., Stejskal V. The effects of a prolonged photoperiod and light source on growth, sexual maturation, fin condition, and vulnerability to fungal disease in brook trout Salvelinus fontinalis // Aquaculture Research. – – V.50. – №1. – P.256–267. doi:10.1111/are.13891
66. Madison B. N., Tavakoli S., Kramer S., Bernier N. J. Chronic cortisol and the regulation of food intake and the endocrine growth axis in rainbow trout // The Journal of endocrinology. – – V.226. – №2. – P.103–119. doi:10.1530/JOE–15–0186
67. Mallik R., Wcisel D. J., Near T. J., Yoder J. A., Dornburg A. Investigating the Impact of Whole-Genome Duplication on Transposable Element Evolution in Teleost Fishes // Genome biology and evolution. – – V.17. – №1. – evae272. doi:10.1093/gbe/evae272
68. Mennigen J. A., Magnan J., Touma K., Best C., Culbert B. M., Bernier N. J., Gilmour K. M. Social status-dependent regulation and function of the somatotropic axis in juvenile rainbow trout // Molecular and Cellular Endocrinology. – –V.554. – 111709. doi:10.1016/j.mce.2022.111709
69. Morro B., Balseiro P., Albalat A., Pedrosa C., Mackenzie S., Nakamura S., et al. Effects of different photoperiod regimes on the smoltification and seawater adaptation of seawater-farmed rainbow trout (Oncorhynchus mykiss): Insights from Na+, K+–ATPase activity and transcription of osmoregulation and growth regulation genes // Aquaculture. – – V.507. – P.282–292. doi: 10.1016/j.aquaculture.2019.04.039
70. Naderi M., Keyvanshokooh S., Salati A.P., Ghaedi A. Effects of chronic high stocking density on liver proteome of rainbow trout (Oncorhynchus mykiss) // Fish physiology and biochemistry. – – V.43. – №5. – P.1373–1385. DOI:10.1007/s10695–017–0378–8
71. Nemova N.N., Kantserova N.P., Lysenko L.A. The Traits of Protein Metabolism in the Skeletal Muscle of the Teleost Fish // Journal of Evolutionary Biochemistry and Physiology. – – V.57. – №3. – P.626–645. doi:10.1134/S0022093021030121
72. Nevoux M., Marie A. D., Raitif J., Baglinière J. L., Lorvelec O., Roussel J. M. Where does the rainbow end? A case study of self-sustaining rainbow trout Oncorhynchus mykiss populations in tropical rivers // bioRxiv. – – 2022–06. doi:10.1101/2022.06.21.497001
73. Noori A., Mojazi Amiri B., Mirvaghefi A., Rafiee G., Kalvani Neitali B. Enhanced growth and retarded gonadal development of farmed rainbow trout, Oncorhynchus mykiss (Walbaum) following a long‐day photoperiod // Aquaculture Research. – – V.46. – №10. – P.2398–2406. doi:10.1111/are.12398
74. Păpuc T., Cocan D., Constantinescu R., Răducu C., Lațiu C., Uiuiu P., Muntean G., Andrada Ihuț A., Ladoși D., Ladoși I., Becze A., Mireșan V. Blood parameters of rainbow trout Oncorhynchus mykiss (Walbaum, 1792) fed diets supplemented with natural phytoadditives during the cold season // Scientific Papers. Series D. Animal Science. – –V.68. – №1.
75. Pérez-Sánchez J., Simó-Mirabet P., Naya-Català F., Martos-Sitcha J. A., Perera E., Bermejo-Nogales A., Benedito-Palos L., Calduch-Giner J. A. Somatotropic axis regulation unravels the differential effects of nutritional and environmental factors in growth performance of marine farmed fishes // Frontiers in endocrinology. – –V.9. – P.687–711. doi:10.3389/fendo.2018.00687
76. Philip A.M., Vijayan M.M. Stress-immune-growth interactions: cortisol modulates suppressors of cytokine signaling and JAK/STAT pathway in rainbow trout liver // PLoS One. – – V.10. – №6. – e0129299. doi:10.1371/journal.pone.0129299
77. Polaz S.V., Biaspaly A.V., Dzegtyarik S.M., Slabadnitskaya H.U. Influence of some stress factors on cortisol indicators of Oncorhynchus mykiss // Belarus Fish Industry Problems. – – V.35. – P.232–238. (In Russ.).
78. Poppinga J., Kittilson J., McCormick S.D., SheridanтA. Effects of somatostatin on the growth hormone-insulin-like growth factor axis and seawater adaptation of rainbow trout (Oncorhynchus mykiss) // Aquaculture. – 2007. –V.273. – №2–3. – P.312–319. doi:10.1016/j.aquaculture.2007.10.021
79. Reid R. M., Turkmen S., Cleveland B. M., Biga P. R. Direct actions of growth hormone in rainbow trout, Oncorhynchus mykiss, skeletal muscle cells in vitro // Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology. – – V.297. –111725. doi:10.1016/j.cbpa.2024.111725
80. Raine J.C., Hua K., Bureau D.P., Vijayan M.M., Leatherland J.F. Influence of ration level and rearing temperature on hepatic GHR1 and 2, and hepatic and intestinal TRα and TRβ gene expression in late stages of rainbow trout embryos // Journal of Fish Biology. – 2007. – V.71(1). – P.148-162. doi:10.1111/j.1095-8649.2007.01476.x
81. Reindl K.M., Sheridan M.A. Peripheral regulation of the growth hormone-insulin-like growth factor system in fish and other vertebrates // Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology. – –V.163. – №3–4. P.231–245. doi:10.1016/j.cbpa.2012.08.003
82. Rhodes S.J., Rosenfeld M.G. Molecular involvement of the Pit-1 gene in anterior pituitary cell commitment. Journal of Animal Science. – 1996. – V.74(2). P.94–106. doi:10.2527/1996.74suppl_294x
83. Rodin M.A., Kuznetsova M.V., Krupnova M.Y., Kuritsyn A. E., Nemova N. N. Biochemical and Molecular–Genetic Growth Indices of Rainbow Trout (Oncorhynchus mykiss Walb.) under the Conditions of the Southern Region of the Russian Federation in a Long-Term Study // Biology Bulletin. – – V.52. – №3. – P.78. doi:10.1134/S1062359024613922
84. Rousseau K., Dufour S. Phylogenetic evolution of the neuroendocrine control of growth hormone: contribution from teleosts // Cybium. – – V.28. –№3. – P.181–198.
85. Saha A., Samanta M., kumar Barman H., Giri S.S. New insights into spexin and pituitary adenylate cyclase-activating polypeptide (PACAP) in regulating fish reproduction // Aquaculture and Fisheries. – –V.9. – №3. – P.411–416. doi:10.1016/j.aaf.2023.08.008
86. Sakamoto T., Hirano T. Expression of insulin-like growth factor I gene in osmoregulatory organs during seawater adaptation of the salmonid fish: possible mode of osmoregulatory action of growth hormone // Proceedings of the National Academy of Sciences. – – V.90. – №5. – P.1912–1916. doi:10.1073/pnas.90.5.1912
87. Shcherbakov Y.S., Terletskiy V.P. The search for associations of rainbow trout perfomance with single nucleotide polymorphisms in the EGR1, FAM60A, and BCL2L11 genes // International Research Journal. – – V.1. – №127. – P.28–31. (In Russ.) doi:10.23670/IRJ.2023.127.92
88. Shulgina N.S., Churova M.V., Nemova N.N. Effect of the photoperiod on the growth and development of salmonids in northern latitudes // Biology Bulletin Reviews. – – V.82. – №1. – P.68–80. doi:10.31857/S0044459621010073
89. Singh A.K. 2024. Coldwater Aquaculture Scenario of the World // Aquaculture and Conservation of Inland Coldwater Fishes. Singapore: Springer. P.27– doi:10.1007/978–981–97–1790–3_2
90. Tekeli H., Bildik A. Effects of age and seasonal temperatures on cortisol levels and GHR, IGF-I, and IGF-II expressions in rainbow trout (Oncorhynchus mykiss) // Journal of the Hellenic Veterinary Medical Society. – – V.74. – №2. – P.5539–5546. doi:10.12681/jhvms.27769
91. Tesina P., Lessen L. N., Buschauer R., Cheng J., Wu C. C., Berninghausen O., Buskirk A. R., Becker T., Beckmann R., Green R. Molecular mechanism of translational stalling by inhibitory codon combinations and poly(A) tracts // The EMBO journal. – –V.39. – №3. – e103365. doi:10.15252/embj.2019103365
92. Turgut N., Tıpırdamaz S., Yalçın H. Sex Determination in Young and Adult Rainbow Trout Using Geometric Morphometrics Analysis // Kahramanmaraş Sütçü İmam Üniversitesi Tarım ve Doğa Dergisi. – – V.27. – №2. – P.533–541. doi:10.18016/ksutarimdoga.vi.1518236
93. Tyshchenko V.I., Shcherbakov Y.S., Nikolaeva O.A., Terletsky V.P. Identification of single nucleotide polymorphisms in BMP-2 gene and their associations with productive traits in Rainbow Trout // Agrarian science. – –V.1. – №8. – P.145–149. (In Russ.) doi:10.32634/0869–8155–2024–385–8–145–149
94. Urban-Sosa V. A., Ávila-Mendoza J., Carranza M., Martínez-Moreno C. G., Luna M., Arámburo C. Differential peptide-dependent regulation of growth hormone (GH): A comparative analysis in pituitary cultures of reptiles, birds, and mammals // Heliyon. – – V.10. – №12. – e33060. doi:10.1016/j.heliyon.2024.e33060
95. Valenzuela A., Rodríguez I., Schulz B., Cortés R., Acosta J., Campos V., Escobar-Aguirre S. Effects of continuous light (LD24:0) modulate the expression of lysozyme, mucin and peripheral blood cells in rainbow trout // Fishes. – –V.7. – №1. – P.28–38. doi:0.3390/fishes7010028
96. Valenzuela C.A., Ponce C., Zuloaga R., González P., Avendaño-Herrera R., Valdés JA, Molina A.  Effects of crowding on the three main proteolytic mechanisms of skeletal muscle in rainbow trout (Oncorhynchus mykiss) // BMC veterinary research. – – V.16. – №1. – P.294–305. doi:10.1186/s12917–020–02518–w
97. Velázquez J., Rodríguez-Cornejo T., Rodríguez-Ramos T., Pérez-Rodríguez G., Rivera L., Campbell,J. H., Al-Hussinee L., Carpio Y., Estrada M.P., Dixon B. New Evidence for the role of pituitary adenylate cyclase-activating polypeptide as an antimicrobial peptide in teleost fish // Antibiotics. – – V.12. – №10. –P.1484–1503. doi:10.3390/antibiotics12101484.
98. Vélez E. J., Lutfi E., Azizi S., Perelló M., Salmerón C., Riera-Codina M., et al. Understanding fish muscle growth regulation to optimize aquaculture production // Aquaculture. – – V.467. – P.28–40. doi:10.1016/j.aquaculture.2016.07.004
99. Very N.M., Kittilson J.D., Norbeck L.A., Sheridan M.A. Isolation, characterization, and distribution of two cDNAs encoding for growth hormone receptor in rainbow trout (Oncorhynchus mykiss) // Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology. – – V.140. – №4. – P.615–628. doi:10.1016/j.cbpc.2004.12.008
100. Walock C. N., Kittilson J. D., Sheridan,M. A. Characterization of a novel growth hormone receptor-encoding cDNA in rainbow trout and regulation of its expression by nutritional state // Gene. – – V.533. – №1. – P.286–294. doi: 10.1016/j.gene.2013.09.046
101. Weber G.M. Effects of IGF1 and IGF2 on in vitro ovarian follicle maturation in rainbow trout, Oncorhynchus mykiss // Fishes. – –V.8. – №7. – P.367. doi:10.3390/fishes8070367
102. Weber G.M., Ma H., Birkett J., Cleveland B.M. Effects of feeding level and sexual maturation on expression of genes regulating growth mechanisms in rainbow trout (Oncorhynchus mykiss) // Aquaculture. – – V.551. – 737917. doi:10.1016/j.aquaculture.2022.737917
103. Xiang K., Yang Q., Liu M, Yang, X., Li J., Hou Z., Wen H. Crosstalk between growth and osmoregulation of GHRH-SST-GH-IGF axis in triploid rainbow trout (Oncorhynchus mykiss) // International Journal of Molecular Sciences. – – V.23. – №15. – P.8691–8708. doi:10.3390/ijms23158691
104. Xu H., Shi C., Ye Y., Mu C., Wang C. Photoperiod-independent diurnal feeding improved the growth and feed utilization of juvenile rainbow trout (Oncorhynchus mykiss) by inducing food anticipatory activity // Frontiers in Marine Science. – – V.9. – 1029483. doi:10.3389/fmars.2022.1029483
105. Yada T., Muto K., Azuma T., Hyodo S., Schreck C. B. Cortisol stimulates growth hormone gene expression in rainbow trout leucocytes in vitro // General and Comparative Endocrinology. – –V.142. – №1–2. P.248–255. doi:10.1016/j.ygcen.2005.01.008
106. Yang B.Y., Chan K. M., Lin C.M., Chen T.T. Characterization of rainbow trout (Oncorhynchus mykiss) growth hormone 1 gene and the promoter region of growth hormone 2 gene. Archives of biochemistry and biophysics. – 1997. – 340(2). – P.359–368. doi:10.1006/abbi.1997.9930
107. Yang B. Y., Greene M., Chen T. T. Early embryonic expression of the growth hormone family protein genes in the developing rainbow trout, Oncorhynchus mykiss // Molecular Reproduction and Development: Incorporating Gamete Research. – –V.53. – №2. – P.127–134. doi:10.1002/(SICI)1098–2795(199906)53:2<127::AID–MRD1>3.0.CO;2–H
108. Yue G.H. Recent advances of genome mapping and marker‐assisted selection in aquaculture // Fish and fisheries. – – V.15. – №3. – P.376–396. doi:10.1111/faf.12020
109. Zahedi S., Akbarzadeh A., Mehrzad J., Noori A., Harsij M. Effect of stocking density on growth performance, plasma biochemistry and muscle gene expression in rainbow trout (Oncorhynchus mykiss) //Aquaculture. – –V.498. – P.271–278. doi:10.1016/j.aquaculture.2018.07.044
110. Zhang M., Shi Y., Wang Z, Chen Z., Li X., Xu W., Wang N. Genome-Wide Identification and Characterization of gh/prl/sl Family in Cynoglossus semilaevis // International Journal of Molecular Sciences. – – V.26. – №4. – P.1585–1604. doi:10.3390/ijms26041585
111. Zhang Z., Lu K., Liang X. F., Li J., Tang S., Zhang Y., Cai W., Xiao Q.,  Zhang Q. Effects of early low temperature exposure on the growth, glycolipid metabolism and growth hormone (gh) gene methylation in the late stage of Chinese perch (Siniperca chuatsi) // Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology. – – V.259. – 110705. doi:10.1016/j.cbpb.2021.110705.

Статья поступила в редакцию 15 декабря 2025 г.

Принята к печати 19 декабря 2025 г.

Received December 15, 2025

Accepted December 19, 2025