Gen. Comp. Endocrinol. [JOURNAL]
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200 papers
PFOA effects on osteoblast differentiation: Involvement of oxidative stress and endocannabinoid receptors.
Sella F, Giommi C, Carbonari D … +2 more , Lombó M, Carnevali O
Gen Comp Endocrinol · 2026 Apr · PMID 41997379 · Publisher ↗
Perfluorooctanoic acid (PFOA), a persistent perfluoroalkyl substance (PFAS), has been implicated in bone mineral density loss and defective osteogenesis. In this study, by employing human fetal osteoblast (hFOB1.19), we...
Perfluorooctanoic acid (PFOA), a persistent perfluoroalkyl substance (PFAS), has been implicated in bone mineral density loss and defective osteogenesis. In this study, by employing human fetal osteoblast (hFOB1.19), we investigated whether PFOA interferes with osteoblast differentiation by altering the transcription of genes involved in osteogenesis, and protein levels of oxidative stress defense and cannabinoid receptors (CBs). The hFOB 1.19 were exposed to increasing PFOA concentrations (1-100 µM) for seven days, representing supra-environmental concentration commonly used in mechanistic in vitro studies. Osteogenic markers were then evaluated at transcriptional level together with matrix deposition, and the results were compared to an untreated control group. Exposure to PFOA at 10 µM increased the expression of osteocalcin (BGLAP) encoding for a protein involved in calcium deposition. Catalase (CAT) protein levels were upregulated at 1 µM PFOA, while superoxide dismutase (SOD1) did not change, suggesting a selective antioxidant response to oxidative perturbation. Notably, this increase in CAT correlated with a trend toward RUNX2 upregulation, possibly representing a compensatory mechanism to preserve differentiation under oxidative stress. In addition, the highest concentration of PFOA modulated the endocannabinoid system (ECS), reducing CB1 and CB2 protein levels. Despite these molecular changes, Alizarin Red staining revealed a borderline and not statistically significant enhanced calcium deposition only at 50 µM PFOA, suggesting potentially aberrant mineralization. Overall, our findings suggest that PFOA perturbs osteoblast differentiation through oxidative stress-linked mechanisms and CBs modulation, with catalase emerging as a key protective mediator of osteogenic competence under environmental contaminants. Furthermore, the observed dysregulation of CB1 and CB2 receptors indicates that the ECS itself may represent a direct target of PFOA action in osteoblasts.
Diurnal variation of plasma corticosterone, glucose, and protein levels in captive rice field frog Hoplobatrachus rugulosus (Wiegmann, 1834).
Apibanpathomrat A, Khonsue W, Jantawongsri K … +1 more , Kitana N
Gen Comp Endocrinol · 2026 Apr · PMID 41997378 · Publisher ↗
Corticosterone (CORT) is a major stress hormone in amphibians that shows rhythmic daily variation and plays a central role in metabolic regulation. Those responses can potentially be altered under captive conditions. Thi...
Corticosterone (CORT) is a major stress hormone in amphibians that shows rhythmic daily variation and plays a central role in metabolic regulation. Those responses can potentially be altered under captive conditions. This study aimed to investigate daily variations in plasma CORT, glucose, and total protein (TP) levels in captive Hoplobatrachus rugulosus during wet and dry seasons. Blood samples were collected every 4 h over a 24-h period from adult male and female frogs and analyzed, revealing sex-specific diurnal and seasonal patterns in these physiological parameters. In males, plasma CORT levels exhibited significant diurnal variation in both seasons, with lower levels at night compared to the afternoon, whereas females showed significant seasonal differences in CORT levels. Glucose levels differed between seasons in males, suggesting seasonal changes in metabolic demand, while females showed diurnal variation during the wet season, likely associated with feeding schedules. The TP levels varied seasonally in males, whereas females displayed diurnal variation during the dry season, indicating sex-specific strategies in energy allocation and physiological regulation under contrasting environmental conditions. These findings highlight seasonal and sex-specific physiological adjustments in captive H. rugulosus, providing insights that could improve frog rearing practices in Thailand.
What's in a name? Nomenclature inconsistencies in the corticotropin-releasing factor/hormone system across time and taxa.
Culbert BM, Bernier NJ
Gen Comp Endocrinol · 2026 Apr · PMID 41980671 · Publisher ↗
The use of clear, consistent, and specific terminology is important for maximizing the accessibility of scientific knowledge across all academic disciplines, including endocrinology. Yet, the nomenclature used to describ...
The use of clear, consistent, and specific terminology is important for maximizing the accessibility of scientific knowledge across all academic disciplines, including endocrinology. Yet, the nomenclature used to describe the primary hypophysiotropic neuropeptide responsible for centrally regulating rates of corticosteroid synthesis in vertebrates is inconsistent. Researchers use the terms "corticotropin-releasing factor (CRF)" and "corticotropin-releasing hormone (CRH)" at almost equal frequency. While this may seem relatively minor, it highlights broader nomenclature issues that exist within this important neuropeptide family. Indeed, most neuropeptides in this family have had multiple names since their initial discovery and/or are described using different names in different taxa. This creates considerable confusion among students and researchers unfamiliar with this literature. In this review, we provide a historical perspective addressing how and why the nomenclature for these neuropeptides has changed. We also provide context for why some inconsistencies (e.g., CRF vs CRH) will likely continue to persist. Overall, our goal is to increase accessibility and remove barriers which may discourage research on this important neuropeptide family.
Hormonal actions of relaxin-like gonad-stimulating peptide in starfish.
Mita M
Gen Comp Endocrinol · 2026 Apr · PMID 41966310 · Publisher ↗
Oocyte maturation is a process that occurs in the ovaries, where immature oocytes resume meiosis to attain competence for normal fertilization after ovulation/spawning. Gonadotropic hormone (GTH) is the initial trigger o...
Oocyte maturation is a process that occurs in the ovaries, where immature oocytes resume meiosis to attain competence for normal fertilization after ovulation/spawning. Gonadotropic hormone (GTH) is the initial trigger of this process. Relaxin-like gonad-stimulating peptide (RGP) in starfish is the first neuropeptide hormone with GTH-like activity identified in invertebrates. RGP is a heterodimeric peptide consisting of A- and B-chains, belonging to the insulin superfamily, particularly the relaxin group. This review describes the mechanism of action of RGP from oocyte maturation to ovulation in starfish. Recently, RGP has been found to be distributed in the nerve plexus around gonoducts connecting gonads and gonopores. This suggests that RGP secreted from the gonoducts stimulates ovarian follicle cells and testicular interstitial cells to produce the maturation-inducing hormone, 1-methyladenine (1-MeAde). RGP acts on receptors, G proteins, and adenylyl cyclase in these target cells, increasing intracellular cyclic AMP levels and resulting in 1-MeAde production. The RGP receptor is a rhodopsin-like G protein-coupled receptor which is homologous to human relaxin family peptide receptor and Drosophila leucine-rich repeat G protein-coupled receptor 3. Interestingly, the Gαs protein, which is important for RGP signal transduction, is absent from follicle cells surrounding the small oocytes before the breeding season, but is expressed during the breeding season. Neither RGP nor 1-MeAde is directly involved in the gonadal contraction required for ovulation. While some neuropeptides may be involved in gonadal contraction and relaxation, 1-MeAde likely induces the secretion of non-neuronal acetylcholine in the ovaries and testes, resulting in muscle contraction of the gonadal wall to release mature oocytes and sperm.
Photoperiod effects on the expression of deep brain photoreceptors and gonadotrophin genes are sex- and age-dependent in Pekin ducks.
Oluwagbenga EM, Wilson N, Fraley GS
Gen Comp Endocrinol · 2026 Apr · PMID 41962872 · Publisher ↗
Birds rely on a specialized set of photoreceptive neurons called deep brain photoreceptors (DBPs) for the detection of light signals which are then integrated to modulate the expression of gonadotropin hormones. Therefor...
Birds rely on a specialized set of photoreceptive neurons called deep brain photoreceptors (DBPs) for the detection of light signals which are then integrated to modulate the expression of gonadotropin hormones. Therefore, we want to investigate DBPs expression, melanopsin (OPN 4), neuropsin (OPN5), and vertebrate ancient opsin (VAOpn), and their regulation of gonadotropin releasing hormone (GnRH) and gonadotropin inhibitory hormone (GnIH) genes in regards to sex and age in Pekin ducks. 460 hatchlings were randomly allocated to 4 rooms and exposed to 24 h light (LL) or photostimulation (PS; n = 30 hens and 7 drakes/pen; 4 pens/treatment) for 19 weeks. Ducks were euthanized via an intravenous injection of sodium pentobarbital (Fatal Plus; 396 mg/mL/kg body weight) at weeks 0, 5, 10, and 19 (n = 6/sex/treatment/timepoint) for brain sample collection which was further hemisected into diencephalon. Gene expressions of OPN 4, OPN5, and VAOpn, GnRH, and GnIH were quantified using qRT-PCR. In the hens, OPN4 expression was higher (p < 0.05) in LL compared to PS at week 0, suggesting a rapid transcriptional response to continuous light but no difference in OPN5 expression. VAOpn expression was reduced (P < 0.05) in PS compared to LL at week 10 in the hens. In parallel, GnRH expression was higher (p < 0.05) under LL compared to PS at week 19, peaked at week 0 in both treatments and declined (p < 0.05) thereafter in the hens. In contrast, GnIH expression increased (p < 0.01) with age in both sexes, and was lower in the PS hens compared to LL hens at week 10. These findings demonstrate photoperiod-dependent variation in DBPs alongside GnRH and GnIH transcription which is consistent with a possible involvement in sex-specific reproductive development in ducks.
Peripheral and central regulation of thyroid status in teleost fish with particular reference to tetraploid juvenile salmonids and parr-smolt transformation.
Eales JG, Copeland M, MacKenzie DS
Gen Comp Endocrinol · 2026 Apr · PMID 41956167 · Publisher ↗
Mammalian thyroid status is governed by thyroid secretion of L-thyroxine (T) as a prohormone that is monodeiodinated in peripheral tissues to bioactive T (3,5,3'-triiodo-l-thyronine). T secretion is controlled by the hyp...
Mammalian thyroid status is governed by thyroid secretion of L-thyroxine (T) as a prohormone that is monodeiodinated in peripheral tissues to bioactive T (3,5,3'-triiodo-l-thyronine). T secretion is controlled by the hypothalamic-pituitary-thyroid (HPT) axis (central control) whereas T availability to target cells depends mainly on mechanisms in extrathyroidal tissues such as cellular transport and deiodination (peripheral control). Does this model apply to poikilothermic teleost fish which in contrast to homeothermic mammals may show major surges in plasma T due to season, feeding, reproductive state or stressors? We have evaluated the contributions of central and peripheral mechanisms to fish thyroid status in light of recent discoveries employing both traditional endocrine approaches and more modern molecular biological techniques, focusing primarily on salmonid species which may undergo a unique thyroid-implicated premigratory parr-smolt transition (PST), and which as tetraploids may express multiple paralogs of regulatory peptides. Most teleost research has focused on peripheral control by the three classic deiodinases (D1, D2 and D3). In salmonids they determine systemic (D1, D2) and tissue-specific (D2) T generation from T and the equally critical T and T degradations (D1, D3). Tetraploid salmonids may express up to four paralogs for a given deiodinase, providing the potential for species-specific or tissue-specific T production, curtailment of T action, or iodine recapture. Critical as they appear, salmonid deiodinases do not function in isolation but in concert with, and dependence on, TH plasma transport, cell-membrane translocation, hepatic conjugation, biliary excretion and gastrointestinal metabolism. Two rainbow trout properties are particularly distinct from the mammalian model: i) T, but not T, exchanges rapidly between plasma and erythrocytes permitting plasma T stability despite marked acute changes in plasma T and ii) in contrast to ingested T, which is unavailable from food due to complete gastrointestinal deiodination, ingested T contributes to the plasma T pool. Thus the teleost liver, poised at the confluence of exogenous and endogenous T sources, may play a strategic role through its TH biliary excretion, deiodination and other pathways in regulating systemic T availability involved in anabolic/catabolic balance and somatic growth. A major consequence of ingested T degradation is the exclusive delegation of T availability to the HPT axis. Since mammalian TSH consistently stimulates teleost T secretion a mammal-like HPT central control model has been assumed. However, teleost HPT function differs from that of homeotherms in both its hypothalamic control and response to external stimuli. T secretion could be regulated mainly by T negative feedback with the HPT axis playing a subsidiary role of merely ensuring adequate T substrate for regulated peripheral deiodination to proceed. However, this does not account for the notable surges in salmonid plasma T and implies resetting of the HPT 'thyrostat'. Thus the role of central TSH control in the regulation of plasma T changes remains unclear, awaiting further characterization of endogenous TSH secretion. Furthermore, discoveries of TSH-subunit and TSH-receptor expression in piscine peripheral tissues such as the CNS, liver, and gonad require reassessment of TSH function with a focus not only on its traditional endocrine actions but also on its potential as a paracrine regulator of TH action in peripheral tissues. In conclusion, while there are many similarities in thyroid regulation between mammals and salmonids there are also key differences. These likely stem from the evolution of homeothermy, the constraints of terrestrial iodine availability and a plasticity in salmonid peripheral and central control resulting from tetraploidy.
Understanding thyroid hormone receptor function in controlling developmental timing and rate in Xenopus: A journey from biochemistry and molecular biology to genetics.
Shi YB
Gen Comp Endocrinol · 2026 Apr · PMID 41956166 · Full text
Anuran metamorphosis has long been used as a model to study thyroid hormone (T3) function during vertebrate development. The cloning of T3 receptor (TR) in the late 1980 s opened a door for using anuran metamorphosis to...
Anuran metamorphosis has long been used as a model to study thyroid hormone (T3) function during vertebrate development. The cloning of T3 receptor (TR) in the late 1980 s opened a door for using anuran metamorphosis to address some fundamental questions on T3 action in development that were difficult to ask or address in mammalian models. Here, I will review some of the studies ranging from biochemical and molecular investigations to more recent genetic studies that have not only uncovered novel and critical roles of TR in regulating adult organ development and larval tissue resorption/remodeling but also revealed in vivo mechanisms of T3 action. I will focus mainly on the work involving two highly related species, the allotetraploid Xenopus laevis and diploid Xenopus tropicalis, which offer many unique but complementary advantages for in vivo studies of TR function.
Discovery and pleiotropic effects of a "Feeding Circuit-Activating Peptide"-type neuropeptide in the mollusk Lymnaea stagnalis.
Osugi T, Szántó A, Svigruha R … +7 more , Tacey TL, Bozsó Z, Tóth GK, Matsubara S, Satake H, Fodor I, Pirger Z
Gen Comp Endocrinol · 2026 Apr · PMID 41951185 · Publisher ↗
Neuropeptides play a central role in the regulation of animal physiology and behavior. Mollusks have been pivotal in the discovery of neuropeptide signaling, yet the diversity and functional roles of neuropeptides remain...
Neuropeptides play a central role in the regulation of animal physiology and behavior. Mollusks have been pivotal in the discovery of neuropeptide signaling, yet the diversity and functional roles of neuropeptides remain incompletely understood across the phylum. In this study, we identified and characterized a novel Feeding Circuit-Activating Peptide (FCAP)-type neuropeptide in the widely used molluscan model, the great pond snail (Lymnaea stagnalis). Using mass spectrometry imaging (MSI), we detected a new peptide, ALDLSGGFNVHGW, which differs by a single amino acid from FCAPb (ALDLSGGFQVHGW) of Aplysia californica. Sequence analysis revealed that the FCAP precursor of L. stagnalis contains 20 copies of ALDLSGGFNVHGW and one copy of an active peptide identical to Ap-FCAPb. Subsequent MSI analysis indicated that ALDSLGGFNVHGW is the main active FCAP-type peptide, predominantly localized in the anterior lobe of the right cerebral ganglion and sparsely in the buccal ganglia. Furthermore, ALDLSGGFNVHGW co-localized with APGWamide, but not with FMRFamide or cardioexcitatory peptide. Behavioral assays demonstrated dose-dependent, pleiotropic effects of ALDLSGGFNVHGW: transient suppression of feeding, delayed enhancement of locomotor activity, and robust stimulation of egg-laying. Together, these anatomical, molecular, and behavioral data support the view that peptides of the FCAP family are not restricted to feeding modulation but instead act as multifunctional regulators. Future studies, including identification of the receptor(s) that mediate the effects of FCAP-type peptides, are required to deepen our understanding of their functions and evolutionary relationships with neuropeptides in other phyla.
Constitutive activation of MC1R in the large-billed crow (Corvus macrorhynchos) and its potential role in black plumage.
Nakano S, Tashiro Y, Fukuchi H … +2 more , Aizawa S, Takeuchi S
Gen Comp Endocrinol · 2026 Apr · PMID 41951184 · Publisher ↗
Melanin-based plumage coloration in birds is largely regulated by the melanocortin 1 receptor (MC1R), a G protein-coupled receptor that promotes eumelanin synthesis via cAMP signaling. In domestic chickens, constitutivel...
Melanin-based plumage coloration in birds is largely regulated by the melanocortin 1 receptor (MC1R), a G protein-coupled receptor that promotes eumelanin synthesis via cAMP signaling. In domestic chickens, constitutively activating mutations such as the MC1R^E (E92K) allele cause melanistic phenotypes, demonstrating that persistent MC1R activation can drive generalized darkening. However, to our knowledge, no experimental study has directly demonstrated constitutive MC1R activation in wild birds exhibiting uniformly black plumage. We investigated the sequence and signaling properties of MC1R from the Large-billed Crow (Corvus macrorhynchos), a species with strongly eumelanin-dominant plumage. Crow MC1R exhibited elevated basal cAMP signaling and minimal responsiveness to α-melanocyte-stimulating hormone (α-MSH) in both stable Chinese hamster ovary (CHO-K1) cells and transient CRE-luciferase assays in HEK293T cells, demonstrating ligand-independent activation comparable to that observed in the melanizing chicken MC1R^E (E92K) allele. Comparative sequence analysis identified multiple substitutions conserved across Corvus species. Among these, E12K and E18K were functionally evaluated based on prior associations with melanism in other birds. Although E12K modestly increased basal signaling in chicken MC1R, E18K alone or in combination with E12K did not reproduce crow-level constitutive activity, and reciprocal substitutions in crow MC1R failed to abolish ligand-independent activation. These findings demonstrate that crow MC1R possesses constitutive activity and suggest that this phenotype reflects lineage-specific modifications rather than a single activating substitution. Our results provide experimental evidence that constitutive MC1R activation is a plausible molecular mechanism that may contribute to the black plumage in the Large-billed Crow, although a direct causal relationship remains to be established.
Motilin in amphibians.
Kitazawa T, Kaiya H
Gen Comp Endocrinol · 2026 Apr · PMID 41935755 · Publisher ↗
Motilin was first identified as a gastrointestinal (GI) motility-stimulating peptide and was later shown to mediate the gastric migrating motor complexes (MMCs) in several mammals. Motilin and its receptor have also been...
Motilin was first identified as a gastrointestinal (GI) motility-stimulating peptide and was later shown to mediate the gastric migrating motor complexes (MMCs) in several mammals. Motilin and its receptor have also been identified in non-mammalian vertebrates, including birds, reptiles, amphibians and fish. This discovery has prompted comparative studies on its physiological roles in GI motility. This review focused on amphibian motilin and its role in GI contractions. Like those of mammals, birds, and reptiles, amphibian motilin is a 22-amino-acid peptide produced in the mucosa of the upper small intestine. There is structural variation within amphibians: the N-terminal residue is phenylalanine in Caudata (newts and salamanders) but tyrosine in Apoda (caecilians). Interestingly, motilin receptors have been found in Anura (frogs), yet the endogenous motilin remains undiscovered, even though database searches. This discrepancy leaves the physiological role of the motilin system in anurans a subject of ongoing debate. Functional studies reveal that motilin receptors exist in the central nervous system and the GI tract of vertebrates, and demonstrate an evolutionarily related shift in localization. Motilin receptors are restricted to intestinal mucosal cells in fish but expand to GI smooth muscle cells and enteric neurons in amphibians. This marks a pivotal transition toward the regulation of GI motility. This trajectory culminates in birds and mammals, where receptors are present across the mucosa, smooth muscle, and myenteric plexus. However, the mechanisms driving this receptor expansion, the definitive status of motilin in Anuras, and the specific roles of motilin receptor or motilin-like receptor in these species remain unclear. Addressing these questions will provide deeper insights into the evolutionary endocrinology of the gut-brain axis, establishing amphibian motilin research as a compelling frontier.
Kobayashi Award 2024: Cyclic regulation of the reproductive neuroendocrine system in fish: Using migratory fish as a model.
Ando H
Gen Comp Endocrinol · 2026 Mar · PMID 41881282 · Publisher ↗
Migration involves the coordinated regulation of various physiological functions and behaviors in order to adapt to complex environmental factors in the wild. Migratory fish are valuable models for studying the cyclic re...
Migration involves the coordinated regulation of various physiological functions and behaviors in order to adapt to complex environmental factors in the wild. Migratory fish are valuable models for studying the cyclic regulation of the reproductive neuroendocrine system due to their distinct and tightly timed annual and seasonal reproductive cycles synchronized with changing environmental factors. This review provides an overview of the cyclic regulation of the reproductive neuroendocrine system, focusing on GnRH, kisspeptin and GnIH, in two migratory fish: Pacific salmon, which undertake long-distance spawning migration in the North Pacific Ocean and the grass puffer, which repeatedly migrates to spawn in a coastal area, synchronizing with lunar phases and tidal cycles. Our studies on Pacific salmon revealed that the timeline of sexual maturation is likely common among Pacific salmon, regardless of species or location. During the spawning migration, GnRH3 plays a central role in gonadal maturation and migratory behavior in conjunction with IGF-I and E2. Its action on GTH secretion varies significantly depending on the stage of sexual maturation and the season. In the grass puffer, two different biological clocks, a circatidal clock and a circadian clock, may produce semilunar oscillations, and melatonin may play a role in synchronizing these clocks and the reproductive neuroendocrine system with the lunar phase. Our studies of these two migratory fish species provide valuable insights into how wild animals regulate their reproductive functions in response to periodic changes in diverse environments.
Hair progesterone reflects past reproductive activity in the invasive Pallas's squirrel Callosciurus erythraeus.
Shimamoto T, Furusho K
Gen Comp Endocrinol · 2026 Mar · PMID 41871814 · Publisher ↗
Integrated approaches to physiology and ecology offer powerful tools to assess individual- and population-level health. Although hair glucocorticoid analysis is widely used as a physiological indicator, hair progesterone...
Integrated approaches to physiology and ecology offer powerful tools to assess individual- and population-level health. Although hair glucocorticoid analysis is widely used as a physiological indicator, hair progesterone has recently attracted attention as a potential measure of reproductive health that may integrate information on past reproductive activity. Here, we examined the assay validation and biological utility of hair progesterone analysis as an indicator of long-term reproductive activity in Pallas's squirrel Callosciurus erythraeus. A hair progesterone enzyme immunoassay was validated and used to compare hair progesterone concentrations (HPC) between sexes and age classes. The effects of current and past reproductive activity (pregnancy and number of placental scars), body condition, age, and season (hair non-growth vs. growth season) on adult female HPC were investigated. The analytical assay validation was successful. Adult females had significantly higher HPC than juvenile males, adult males, and juvenile females. Although there was no effect of current reproductive activity, past reproductive activity (as indexed by the number of placental scars) significantly influenced adult female HPC, such that female Pallas's squirrels with more placental scars had higher HPC. There was also a significant positive impact of season on HPC, and females with better body condition tended to have higher HPC. Hair progesterone is therefore an integrative physiological indicator of past reproductive activity in Pallas's squirrels, with potential applications in the prediction of population dynamics to inform the management of this invasive squirrel.
Corrigendum to "Role of gonadal soma-derived growth factor (gsdf) on sex-differentiation in Nile tilapia, Oreochromis niloticus" [Gen. Comp. Endocrinol. 377 (2026) 114884].
Arai T, Tanaka S, Sakon M … +2 more , Gao H, Ijiri S
Gen Comp Endocrinol · 2026 Mar · PMID 41856893 · Publisher ↗
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Corrigendum to "The role of multiple vitellogenins in early development of fishes" [Gen. Comp. Endocrinol. 351 (2024) 114479].
Yilmaz O, Sullivan CV, Bobe J … +1 more , Norberg B
Gen Comp Endocrinol · 2026 Mar · PMID 41850930 · Publisher ↗
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Promiscuous melanocortin receptors in hagfish indicate that receptor function preceded peptide specialization.
Shaughnessy CA, Kuhn EE, Hahs SM … +3 more , Bouyoucos IA, Anderson WG, Dores RM
Gen Comp Endocrinol · 2026 Mar · PMID 41839297 · Publisher ↗
Hagfishes are representatives of the phylogenetically important, early-branching vertebrate lineage Agnatha, and many endocrine signaling systems in this group remain poorly understood. In this study, we provide the firs...
Hagfishes are representatives of the phylogenetically important, early-branching vertebrate lineage Agnatha, and many endocrine signaling systems in this group remain poorly understood. In this study, we provide the first molecular and functional characterization of melanocortin receptors (Mcrs) and their accessory protein (Mrap) in hagfishes. Using genomic and transcriptomic resources from inshore hagfish (Eptatretus burgeri), Pacific hagfish (Eptatretus stoutii), and Atlantic hagfish (Myxine glutinosa), we identified genes encoding two hagfish melanocortin receptors, Mcar and Mcbr, and a single Mrap. When expressed in mammalian cells, both receptors responded to human ACTH(1-24) and α-MSH with similar affinities. Co-expression with Mrap reduced maximal activity of Mcbr but not Mcar and only modestly modulated the ligand sensitivity of either receptor. Gene expression analyses revealed that mcbr and mrap are prominently expressed in the slime gland, a tissue that also transcriptionally expressed the steroidogenic enzymes star and cyp11a1, whereas mcar is most prominently expressed in the brain. These findings suggest that hagfish Mcrs retain broad ligand responsiveness and relative Mrap-independence, consistent with a hypothesized ancestral mode of melanocortin signaling. Although no genes encoding known melanocortin prohormones have yet been identified in hagfish genomes, the presence of functional receptors and tissue-specific expression patterns suggest these genes may have physiological roles and that an as-yet-unidentified ligand may exist in hagfish. Together, these results provide new insight into the organization and evolution of the vertebrate melanocortin system and highlight hagfish as a key model for reconstructing the functional evolution of this essential endocrine signaling pathway.
Establishment of an ELISA system to measure pituitary hormones in teleosts.
Zeng X, Ouyang Y, Shi X … +7 more , Han C, Ke L, Gao Y, Liu X, Yang J, Yang K, Hu G
Gen Comp Endocrinol · 2026 Mar · PMID 41833740 · Publisher ↗
We developed and validated a fluorescence-based competitive enzyme-linked immunosorbent assay (ELISA) for the parallel quantification of four key pituitary hormones-growth hormone (GH), prolactin (PRL), somatolactin alph...
We developed and validated a fluorescence-based competitive enzyme-linked immunosorbent assay (ELISA) for the parallel quantification of four key pituitary hormones-growth hormone (GH), prolactin (PRL), somatolactin alpha (SLα), and somatolactin beta (SLβ)-in grass carp (Ctenopharyngodon idella). The assay utilizes recombinant grass carp hormones as standards and corresponding rabbit polyclonal antibodies, with biotin-avidin-HRP amplification and HPPA-based fluorescence detection. Standard curves demonstrated high linearity and half-maximal inhibitory concentrations (ID) ranging from 8.004 to 18.63 ng/mL. We successfully applied this ELISA to quantify hormone levels in plasma and culture medium from primary pituitary cell culture after stimulation with GHRH, SST, cortisol, and CRH, confirming its ability to detect physiologically relevant changes. This reliable, sensitive, and cost-effective ELISA provides a valuable tool for monitoring endocrine status in grass carp, with potential applications in growth performance assessment, reproductive management, and stress response studies in aquaculture. The method may also be adaptable to other cyprinid species due to high hormone sequence conservation.
Characterization of serotonin receptors Aj5-HTR and Aj5-HTR reveals potential roles in circadian regulation of Apostichopus japonicus.
Wang Y, Liu Y, Ye Z … +8 more , Ge L, Han G, Jiang J, Chen Y, Wang J, Weng J, Yang J, Wang T
Gen Comp Endocrinol · 2026 Mar · PMID 41819218 · Publisher ↗
Serotonin (5-hydroxytryptamine, 5-HT) is an evolutionarily conserved neurotransmitter that mediates neuroendocrine signaling through 5-hydroxytryptamine receptors (5-HTRs). In this study, two 5-HT receptor subtypes, Aj5-...
Serotonin (5-hydroxytryptamine, 5-HT) is an evolutionarily conserved neurotransmitter that mediates neuroendocrine signaling through 5-hydroxytryptamine receptors (5-HTRs). In this study, two 5-HT receptor subtypes, Aj5-HTR and Aj5-HTR, were cloned and functionally characterized from the sea cucumber Apostichopus japonicus. Functional assays demonstrated that both receptors are signaling-competent molecules, exhibiting rapid receptor internalization upon 5-HT stimulation, along with dose-dependent increases in intracellular Ca or cyclic adenosine monophosphate (cAMP) levels and ERK1/2 phosphorylation. Quantitative real-time PCR showed that Aj5-HTR was highly expressed in the nerve ring and tentacles, whereas Aj5-HTR was highly expressed in the Polian vesicle and muscle. Moreover, both receptors exhibited distinct day-night expression rhythms, suggesting subtype-specific involvement in circadian neuroendocrine regulation. In summary, this work expands the repertoire of 5-HTRs in sea cucumbers and provides new insights into their potential roles in circadian neuroendocrine regulation.
Endocrine and immune pathways under pressure: teleost responses to a changing environment.
Eppler E, Bilella A, Link K … +2 more , D'Cotta H, Baroiller JF
Gen Comp Endocrinol · 2026 Mar · PMID 41791583 · Publisher ↗
This minireview talks about how environmental perturbations are affecting fish development and reproductive physiology. It highlights interactions between hormones, growth factors with particular emphasis on the growth h...
This minireview talks about how environmental perturbations are affecting fish development and reproductive physiology. It highlights interactions between hormones, growth factors with particular emphasis on the growth hormone (GH)-insulin-like growth factor (IGF)-axis, and selected cytokines involved in the complex orchestration of reproduction, growth, metabolism and health in teleost fish. Focus is placed on challenges posed by changing water temperature and salinities on fish reproduction and growth, and how these factors influence the GH-IGF-system and immune genes during environmental adaptation. Another focus is placed on chemical pollutants including endocrine disrupting compounds (EDCs) and on mechanistic links with the GH/IGF-immune axis. Finally, we highlight some synergistic effects of EDCs with physical and natural stressors, including pathogens and recent attempts to optimise fish health by dietary additives. This minireview concludes with a discussion of the One Health concept.
Prolactin signaling in the highly osmotolerant Mozambique tilapia, Oreochromis mossambicus.
Seale AP, Cao K, Singh SA … +5 more , Scalambrino B, Chang RJA, Goodearly TR, Merlo RS, Breves JP
Gen Comp Endocrinol · 2026 Mar · PMID 41765146 · Publisher ↗
Teleost fishes maintain hydromineral balance through the hormonal regulation of epithelial ion transport. In the euryhaline, and remarkably osmotolerant Mozambique tilapia (Oreochromis mossambicus), two prolactin (Prl) i...
Teleost fishes maintain hydromineral balance through the hormonal regulation of epithelial ion transport. In the euryhaline, and remarkably osmotolerant Mozambique tilapia (Oreochromis mossambicus), two prolactin (Prl) isoforms, Prl and Prl, are released from the pituitary in response to hyposmotic stimulation to promote branchial ion absorption. Prl and Prl bind two Prl receptors (Prlrs), Prlr1 and Prlr2, which are expressed in the pituitary and key ionoregulatory organs, including the gill. To understand how Prl signaling operates across a range of salinities that reflect their scope for osmotolerance, we exposed Mozambique tilapia to conditions spanning from fresh water (FW; < 0.1‰) to triple-strength seawater (3x SW; 105‰). In the pituitary, prl/prl and prlr1/prlr2 ratios decreased as salinity increased, dropping to levels in 3x SW that were less than 10% of those in FW. Branchial prlr1/prlr2 ratios also decreased with increased salinity, in parallel with effectors of branchial ion uptake, including Na/Cl cotransporter 2 and Na/K ATPase-α1a. While the changes in ratios reflect differences in the reductions of both prl and prl, they also reflect downregulation of prlr1 and upregulation of prlr2 with increasing salinity. Gene transcripts encoding mediators of ion extrusion, such as Na/K/2Cl cotransporter 1a and cystic fibrosis transmembrane conductance regulator 1, were elevated by high-salinity conditions. Our findings indicate that when Mozambique tilapia are exposed to hypersaline conditions, they shift Prl signaling toward Prl and Prlr2 relative to Prl and Prlr1. In turn, the combinatorial nature of isoform-specific responses linked to Prl signaling contributes to both the euryhalinity and exceptional osmotolerance of Mozambique tilapia.
Functional Insights into Bpcreb1 in Bellamya purificata: Expression Dynamics and regulatory Roles during gonadal development.
Ren Y, Jin X, Song J … +4 more , Gu Y, Lv H, Zhang Y, Wang G
Gen Comp Endocrinol · 2026 Feb · PMID 41713793 · Publisher ↗
Cyclic AMP response element-binding protein 1 (CREB1), a conserved bZIP transcription factor, is crucial for animal reproduction. Therefore, this study investigated its role in gonadal development of the freshwater snail...
Cyclic AMP response element-binding protein 1 (CREB1), a conserved bZIP transcription factor, is crucial for animal reproduction. Therefore, this study investigated its role in gonadal development of the freshwater snail Bellamya purificata using qRT-PCR, ISH, RNAi, and DNA methylation analysis. Results revealed that the creb1 CDS (867 bp, 288 aa) features a highly conserved BRLZ domain. Significantly, tissue expression showed markedly higher creb1 transcript levels in testes versus ovaries (p < 0.01). ISH localized enriched mRNA in ovarian oocytes/follicular walls and testicular spermatogonia/sperm. Functionally, efficient RNAi (max. 71.98% silencing) caused acute downregulation of sex genes: female β-catenin, cyp17a1 and sox9 expression fell 27%-34%, while male expression dropped 58%-77%. Critically, prolonged interference induced testicular defects, namely reduced mature sperm and increased spermatogonia, implicating Bpcreb1 in spermatogenesis-potentially via tssk and sox9 regulation. Furthermore, epigenetic analysis found consistently low Bpcreb1 promoter methylation (<5%) in both sexes, yet RNAi did not alter this hypomethylation, hinting at non-methylation regulatory mechanisms. In summary, creb1 demonstrably regulates gonadal development in B. purificata, with a pivotal role in spermatogenesis. Consequently, these findings provide a theoretical foundation for studying its gonadal development and monosex breeding strategies.
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