Gen. Comp. Endocrinol. [JOURNAL]
Sun
200 papers
Identification and expression analysis of three gonadotropin-releasing hormone genes in the lined seahorse (Hippocampus erectus).
Lu Z, Wan S, Lin Q … +1 more , Zhang H
Gen Comp Endocrinol · 2025 Feb · PMID 39914705 · Publisher ↗
Gonadotropin-releasing hormone (GnRH) plays a crucial role in regulating reproductive behavior in vertebrates through the hypothalamus-pituitary-gonad (HPG) axis. Seahorses exhibit unique male pregnancy behavior, making...
Gonadotropin-releasing hormone (GnRH) plays a crucial role in regulating reproductive behavior in vertebrates through the hypothalamus-pituitary-gonad (HPG) axis. Seahorses exhibit unique male pregnancy behavior, making them an interesting subject for investigating the regulatory mechanisms behind this behavior. In this study, we focused on the lined seahorse (Hippocampus erectus) and obtained the full-length cDNA sequences of three GnRH genes: GnRH1, GnRH2, and GnRH3. Notably, we newly identified GnRH1, filling a gap in previous research that had overlooked this subtype. Through a homologous analysis, we found that the core peptide of GnRH1 in lined seahorses is not common in teleosts, while the core peptides of GnRH2 and GnRH3 are conserved. Real-time PCR was performed to determine the tissue expression patterns of these GnRH genes. Our results showed that all three genes were predominantly expressed in the brain, albeit in different regions. Specifically, GnRH1 was mainly expressed in the hypothalamus, GnRH2 in the optic tectum, and GnRH3 in the telencephalon. Expression dynamics indicated a progressive decrease in GnRH2 and a significant surge in GnRH3 during gonadal development, hinting at an alternating regulatory function. Moreover, GnRH1 and GnRH3 expression levels were considerably higher during pregnancy compared to those in pre-pregnancy and post-pregnancy stages, underscoring their critical role in modulating male pregnancy behavior in lined seahorses. Our findings provide insights into the complex interplay of GnRH subtypes in regulating reproductive processes, particularly in the context of male pregnancy behavior in seahorses.
Production of recombinant masu salmon insulin-like growth factor binding protein-2b1 and its action on pituitary cells.
Miura T, Watanabe S, Kizaki R … +3 more , Hasegawa R, Isozaki T, Shimizu M
Gen Comp Endocrinol · 2025 Feb · PMID 39914704 · Publisher ↗
Insulin-like growth factor binding protein (Igfbp)-2b is believed to be a major carrier of circulating Igf-1 in salmonids. We cloned cDNAs of two paralogs of igfbp-2b from the liver of masu salmon and produced recombinan...
Insulin-like growth factor binding protein (Igfbp)-2b is believed to be a major carrier of circulating Igf-1 in salmonids. We cloned cDNAs of two paralogs of igfbp-2b from the liver of masu salmon and produced recombinant Igfbp-2b1 corresponding to the circulating form using a bacterial expression system. The deduced amino acid sequence of masu salmon igfbp-2b1 had a 75.2 % sequence identity with that of masu salmon igfbp-2b2, and 88.7 % and 96.5 % with those of Atlantic salmon and rainbow trout igfbp-2b1, respectively. The coding region of masu salmon igfbp-2b1 cDNA was subcloned into the pET-16b or pET-32a vector and expressed using either a histidine (His)-tag or a thioredoxin (Trx) and His-tag. Recombinant masu salmon (rs) Igfbp-2b1 with the fusion partner was fractionated in the precipitate, solubilized, and isolated using Ni-affinity chromatography. His.rsIgfbp-2b1 and Trx.His.rsIgfbp-2b1 were treated with Factor Xa and enterokinase K, respectively, to remove the fusion partner; only the digestion with enterokinase was successful. After enzymatic digestion, rsIgfbp-2b1 was purified employing reversed-phase high-performance liquid chromatography. The purified rsIgfbp-2b1 was added to a primary culture of masu salmon pituitary cells with or without human (h) IGF-1 to assess its effect on the release of growth hormone (Gh). Although addition of hIGF-1 alone had no effect on Gh release, co-incubation with varying amounts of rsIgfbp-2b1 increased Gh release in a dose-dependent manner. In addition, rsIgfbp-2b1 in the absence of hIGF-1 showed a positive effect on Gh release from salmon pituitary cells. These results suggest that rsIgfbp-2b1 may either have Igf-1-independent action on Gh release or inhibits the suppressive effect of local pituitary Igf-1 on Gh release.
The S6 kinase gene in the fruit fly, Drosophila melanogaster, is essential for metabolic regulation.
Álvarez-Rendón JP, Riesgo-Escovar JR
Gen Comp Endocrinol · 2025 Feb · PMID 39914703 · Publisher ↗
The S6 kinase (S6K) enzyme phosphorylates the S6 ribosomal protein, promoting protein translation and growth. Here we investigated in flies whether hypomorphic conditions in S6K affect intermediate metabolism and oxidati...
The S6 kinase (S6K) enzyme phosphorylates the S6 ribosomal protein, promoting protein translation and growth. Here we investigated in flies whether hypomorphic conditions in S6K affect intermediate metabolism and oxidative homeostasis, besides carbohydrates and growth. We also employed partial activation of the nuclear factor 2 erythroid related factor 2 (Nrf2) in a S6K hypomorphic background and controls. S6K is activated by the target of rapamycin (TOR) kinase, a key kinase regulating metabolism, downstream of the insulin receptor in flies. The insulin pathway is a general anabolic pathway, and key regulator of glucose homeostasis. The Nrf2 counters pro-oxidative conditions, also involved in inflammatory responses and metabolism. The Nrf2 fly homolog is Cap'n'collar C (CncC). We quantified glucose, glycogen, and total lipids in control and different pro-oxidative conditions. We corroborated an accumulation of lipids and carbohydrates in the mutants, and document sexual differences. We document also metabolic and survival differences in the responses to "mild" pro-oxidative conditions in young flies (seven days old), with females being most affected. We compare 10 mM paraquat survival of virgin flies to mated mixed-sex flies housed together. We used females to study transcriptomic differences between wild type and S6k hypomorphs. Results highlight dysregulation of lipid and antioxidant enzymes and genes, in agreement with lipid and oxidative metabolism data. Our results are consistent with the insulin/TOR pathway acting as an integrator of intermediate metabolism and oxidative homeostasis (this last together with the CncC pathway).
Influence of season, capture method, sample age and extraction protocols on the scale cortisol concentrations of three species of freshwater fish.
Ghazal A, Paul R, Tarkan AS … +1 more , Britton JR
Gen Comp Endocrinol · 2025 Feb · PMID 39894175 · Publisher ↗
Scale cortisol concentration (SCC) is increasingly applied as a biomarker of chronic stress in fish, but knowledge gaps remain on how SCC is affected by the sampling season and method of fish capture, the time since samp...
Scale cortisol concentration (SCC) is increasingly applied as a biomarker of chronic stress in fish, but knowledge gaps remain on how SCC is affected by the sampling season and method of fish capture, the time since sample collection, and the cortisol extraction protocol. Here, working with three freshwater fishes (common carp Cyprinus carpio, European chub Squalius cephalus and Northern pike Esox lucius), a robust extraction protocol was developed and then applied to identifying how scale cortisol levels can vary in fish populations according to aspects of the fish capture events. Across five scale cortisol extraction protocols, three provided relatively low yields, so their application would result in erroneously low SCC. Application of the extraction protocol providing the highest yields to scale samples indicated that fish sampled in winter have significantly lower SCC than those collected in spring and summer, while fish captured by angling have significantly lower SCC than fish collected from the same population by electric fishing. There were no significant differences in SCC measured from populations across 40 years, suggesting that archived scales potentially provide a valuable resource for measuring temporal changes in SCC. Future studies based on using scale cortisol for analyses of fish chronic stress should consider these issues in their study designs and evaluations to ensure measured differences in cortisol across time and space are due to differences in how the fish are responding to their environment rather than being an artefact of study design.
An insight into the molecular mechanisms of persistent organic pollutants (POPs) mediated dysregulation of glucose and lipid homeostasis in Heteropneustes fossilis.
Ray SS, Mahapatra A, Gupta P … +2 more , Suman A, Singh RK
Gen Comp Endocrinol · 2025 Feb · PMID 39884368 · Publisher ↗
The study emphasises how ubiquitous persistent organic pollutants (POPs) are and how terrible they are for the environment, specifically because of their tendency to build up in living things and cause a variety of healt...
The study emphasises how ubiquitous persistent organic pollutants (POPs) are and how terrible they are for the environment, specifically because of their tendency to build up in living things and cause a variety of health problems, including diabetes, obesity, and cardiovascular disorders. Due to POPs affinity for lipid-rich tissues, they accumulate in a variety of organs, where they cause metabolic disruption and initiate various anabolic pathways. Studies that use fish as a model organism clarify the metabolic effects of POPs, demonstrating non-adipose lipid accumulation and abnormal glucose homeostasis. Further research on molecular mechanisms shows that POPs interact with gluconeogenic enzymes, causing blood glucose levels to rise. These results are supported by histological and biochemical examinations of fish exposed to POPs, which show changes in lipid composition and cause cellular damage. Molecular docking computational studies demonstrate POPs propensity for binding to gluconeogenic enzymes, providing insight into their potential to promote hyperglycaemia. This study provides a thorough summary of POPs harmful effects on organisms, highlighting their molecular and toxicological, impacts while arguing for better knowledge of their toxicity to vertebrates' developing embryos.
Pharmacological function of melanocortin-3 receptor in goldfish (Carassius auratus).
Yao MX, Du YY, Mo HL … +6 more , Gul Y, Song QC, Yu HX, Liu KX, Wang LX, Li Y
Gen Comp Endocrinol · 2025 Feb · PMID 39793740 · Publisher ↗
The melanocortin-3 receptor (MC3R) was recognized for its critical role in energy metabolism and inflammatory responses in mammals; however, its functions in fish remain poorly understood. This study characterized the mc...
The melanocortin-3 receptor (MC3R) was recognized for its critical role in energy metabolism and inflammatory responses in mammals; however, its functions in fish remain poorly understood. This study characterized the mc3r gene in goldfish, investigating its sequence, tissue distribution, and pharmacological responses. The coding sequence of goldfish mc3r was 975 bp, translating to a 325-amino-acid protein typical of G protein-coupled receptors, with notable conservation across cyprinids. Quantitative PCR analysis revealed high expression levels in the brain. Luciferase assays demonstrated that various agonists, particularly NDP-MSH and ACTH (1-24), effectively activated the cAMP and MAPK/ERK signaling pathways. Furthermore, all agonists tested (α-MSH, β-MSH, ACTH (1-24), and NDP-MSH) significantly inhibited NF-κB signaling, correlating with their activation of cAMP. These findings enhanced our understanding of the melanocortin system's role in regulating energy metabolism and inflammatory processes in teleost fish.
Enhanced expression of Cyp17a1 and production of DHEA-S in the liver of late-pregnant rats.
Ohtsuki Y, Fujiki J, Maeda N … +1 more , Iwano H
Gen Comp Endocrinol · 2025 Feb · PMID 39761705 · Publisher ↗
Cytochrome P450 17A1 (CYP17A1) catalyzes two enzymatic reactions in the biosynthesis of dehydroepiandrosterone (DHEA) from pregnenolone. In pregnant humans, the adrenal gland is responsible for DHEA biosynthesis, which i...
Cytochrome P450 17A1 (CYP17A1) catalyzes two enzymatic reactions in the biosynthesis of dehydroepiandrosterone (DHEA) from pregnenolone. In pregnant humans, the adrenal gland is responsible for DHEA biosynthesis, which is then sulfated by SULT2A1 and released into the bloodstream. This sulfated DHEA is subsequently taken up by the placenta and deconjugated to serve as a precursor for estrogen biosynthesis. The expression of Cyp17a1 is regulated by methylation, typically showing marked interspecies differences, including repression of Cyp17a1 expression in the adrenal gland of rodents. This study focused on the liver, an extragonadal steroidogenic organ showing active sulfate conjugation, as a site for DHEA-sulfate (DHEA-S) biosynthesis during pregnancy in rodents, rather than the adrenal glands. Cyp17a1 expression in rat liver was significantly lower than in the testis, with no differences between sexes. However, Cyp17a1 expression increased significantly before parturition (gestational days [GD] 19-21) compared to late pregnancy (GD 15-18). The Sult2a family were expressed in the livers of both pregnant and non-pregnant rats. We also observed increased DHEA and DHEA-S levels in the liver of pregnant rats before parturition compared to non-pregnant rats, with DHEA-S concentrations being significantly higher at GD 19-21 than at days 15-18. These findings suggest that increased expression of Cyp17a1 in the last trimester enhances DHEA synthesis in the liver, and that DHEA is quickly conjugated by Sult2a. In rodents, the liver may be involved in DHEA-S biosynthesis before parturition, compensating for the repression of Cyp17a1 in the adrenal glands.
Corticosterone, lactate, and circulating leukocyte responses of free-ranging cottonmouth snakes (Agkistrodon piscivorus) vary with the duration and nature of the acute stressor.
Klukowski M, Bailey FC, Cobb VA … +1 more , Pruett JA
Gen Comp Endocrinol · 2025 Jan · PMID 39743021 · Publisher ↗
Exposure to acute stressors can induce multiple physiological changes in vertebrates such as altering circulating hormone and enzyme levels as well as leukocyte counts, and interactions between endocrine and immune funct...
Exposure to acute stressors can induce multiple physiological changes in vertebrates such as altering circulating hormone and enzyme levels as well as leukocyte counts, and interactions between endocrine and immune function may produce suites of physiological changes following acute stress. Previously, we showed that presence of human observers elicited only a weak elevation of plasma corticosterone levels in cottonmouths. Additional variables, however, must be considered to understand if changes in physiological parameters are highly generalized or vary among sexes or with context. Here we tested effects of more intense acute stressors (i.e., confinement for 2 h or 4 h or repeated blood sampling) on plasma corticosterone and lactate concentrations and the number of circulating leukocytes. In addition to testing for sex differences, we also tested two predictions frequently found in the stress physiology literature: (1) because glucocorticoids are involved in mobilization of leukocytes, corticosterone levels should covary with the heterophil to lymphocyte ratio, (2) since one of the major functions of corticosterone is to mobilize energy stores, baseline corticosterone levels (i.e., in immediately bled snakes) should be elevated in individuals in poor body condition. We found that neither sex nor body condition influenced corticosterone responses to confinement. However, repeated blood sampling had a pronounced effect- snakes bled both upon capture and at 2 h had higher corticosterone levels than snakes bled only once at 2 h or even at 4 h. Plasma lactate and the percent azurophils (but not the heterophil to lymphocyte ratio) were also elevated in confined snakes, and both were positively correlated with plasma corticosterone. Our results indicate a pronounced and nuanced effect of confinement stress on the physiology of cottonmouths.
Crosstalk between prolactin, insulin-like growth factors, and thyroid hormones in feather growth regulation in neonatal chick wings.
Nozawa Y, Okamura A, Fukuchi H … +3 more , Shinohara M, Aizawa S, Takeuchi S
Gen Comp Endocrinol · 2025 Jan · PMID 39701429 · Publisher ↗
The elongation of primary feathers in neonatal chicks is delayed by the late-feathering K gene located on the Z chromosome. We recently found that the K gene slows feather growth by reducing the number of functional prol...
The elongation of primary feathers in neonatal chicks is delayed by the late-feathering K gene located on the Z chromosome. We recently found that the K gene slows feather growth by reducing the number of functional prolactin (PRL) receptor (PRLR) dimers. In this study, we investigated the molecular mechanisms by which PRL promotes feather elongation. RT-qPCR and immunohistochemistry analyses revealed that PRLRs are predominantly localized in the pulp rather than in the epidermal layer of the feather follicle. Treatment of primary cultured feather pulp cells with PRL increased the expression of mRNAs for insulin-like growth factors (IGFs; IGF-1 and IGF-2) and type 2 deiodinase (DIO2). Furthermore, treatments with IGF-1 and triiodothyronine (T3) reciprocally enhanced the expression of mRNAs for DIO2 and IGFs. Additionally, BrdU staining in neonatal chicks showed that T3 promoted cell proliferation in both the epidermal layer and pulp cells, while this effect was suppressed by an IGF-1 receptor (IGF1R) inhibitor. These findings suggest a novel model in which PRL upregulates IGFs and DIO2 in feather pulp cells, creating a positive feedback loop between IGFs and T3, ultimately leading to the promotion of cell proliferation in both the epidermal layer and the pulp cells by IGFs. This is the first report proposing crosstalk between PRL, thyroid hormone (TH), and IGFs in feather follicles.
Neuromodulation in the fish brain for reproductive success.
Umatani C
Gen Comp Endocrinol · 2025 Feb · PMID 39701428 · Publisher ↗
In most teleosts, appropriate sexual behaviors and sexual maturation are essential for reproductive success. Most fish display their unique behavioral patterns for mating. These behaviors are thought to be regulated in t...
In most teleosts, appropriate sexual behaviors and sexual maturation are essential for reproductive success. Most fish display their unique behavioral patterns for mating. These behaviors are thought to be regulated in the brain by sex steroid hormones since sexual behaviors are displayed only by sexually mature fish. In addition, recent studies have reported that neuropeptides, which are peptides released from neurons and modulate neural activities via their specific receptors in the brain, also play a key role in regulating sexual behavior. On the other hand, not only sexual behavior but also feeding behavior is important for reproductive function since sexual maturation requires sufficient nutrition. Especially feeding-related peptides, a type of neuropeptides, are thought to modulate feeding behavior. Thus, it is conceivable that neuropeptides are crucial modulators in the brain for reproductive success. This review summarizes recent advances in the knowledge of the neuromodulatory systems involved in sexual and feeding behaviors by neuropeptides and gonadal hormones.
A newly characterized CFSH gene in sex chromosomes is associated with growth instead of sexual development in the prawn Macrobrachium rosenbergii.
Lai XL, Zhang ZH, Chen JY … +5 more , Liu YR, Yun WK, Chen LP, Chen J, Qiu GF
Gen Comp Endocrinol · 2025 Jan · PMID 39672390 · Publisher ↗
Crustacean female sex hormone (CFSH) was first identified as a female eyestalk-specific factor involved in the female sexual development in blue crab. Whether CFSH has conserved role in other decapod species remains to b...
Crustacean female sex hormone (CFSH) was first identified as a female eyestalk-specific factor involved in the female sexual development in blue crab. Whether CFSH has conserved role in other decapod species remains to be clarified. In this study, we identified a CFSH gene (MrCFSH) in the Z and W chromosomes from the prawn Macrobrachium rosenbergii genome. The MrCFSH encodes a protein of 306 amino acids, including a signal peptide, a precursor-associated peptide, and a mature peptide. The MrCFSH transcripts was expressed in the brain, heart, and gonads in both female and male adults. During sexual development, the expression of MrCFSH transcripts gradually increased in female and male juveniles from post-larval 10 (PL10) to PL60 stages but no significant difference between the females and males at the same stages were found. To investigate its potential role in early sexual development, in vivo RNAi experiments were performed by injecting MrCFSH dsRNA into juveniles from PL30 to PL90 stages. After two months of administration, the sexual characteristics of the females and males were not affected, but the growth rate of juveniles was significantly inhibited compared to the control group injected with GFP dsRNA. The body length and body weight was reduced by 25%, 35%, 28%, 26%, and 69%, 76%, 65%, 61% in the juveniles at PL120, PL150, PL180 and PL210 stages, respectively. The body length and weight of males at PL210 stage were reduced by 22% and 54%, and those of females were reduced by 26% and 60%, respectively. Overall, our present study revealed that the MrCFSH is associated with growth instead of sexual development in the prawn M. rosenbergii.
Gonadotropin-releasing hormone II and its receptor regulate motility, morphology, and kinematics of porcine spermatozoa in vitro.
Desaulniers AT, Ross CE, Cederberg RA … +3 more , Lovercamp KW, Lents CA, White BR
Gen Comp Endocrinol · 2025 Jan · PMID 39667624 · Publisher ↗
The second form of gonadotropin-releasing hormone (GnRH-II) and its receptor (GnRHR-II) are abundantly produced within the porcine testis and immunolocalize within the seminiferous tubules, suggesting a role in spermatog...
The second form of gonadotropin-releasing hormone (GnRH-II) and its receptor (GnRHR-II) are abundantly produced within the porcine testis and immunolocalize within the seminiferous tubules, suggesting a role in spermatogenesis and/or sperm function. The objective of this study was to quantify GnRH-II and GnRHR-II abundance within boar reproductive tract tissues and examine their role in porcine sperm function. Immunoblotting revealed GnRHR-II abundance was 12-fold greater (P < 0.0001) within the testis compared with other reproductive organs. Within seminiferous tubules, GnRHR-II prominently immunolocalized to elongating spermatids. In ejaculated spermatozoa, GnRHR-II immunolocalized to the connecting piece. GnRH-II was also detected in seminal plasma, likely originating from the testis as GnRH-II concentrations were greatest in testicular homogenates (P < 0.0001) compared with other reproductive tissues. To assess the effects of GnRH-II/GnRHR-II on sperm function, extended semen samples were treated with GnRHR-II analogues and evaluated via computer-assisted sperm analysis (CASA). In Experiment 1, semen treatment with increasing concentrations of GnRHR-II agonist (D-ala GnRH-II) revealed that two concentrations (0.1 and 100 µM) tended to decrease the percentage of bent sperm tails versus vehicle-treated semen (P < 0.10). In Experiment 2, semen treatment with increasing concentrations of GnRHR antagonist (SB-75/Cetrorelix) indicated that only 10 µM SB-75 impaired CASA metrics compared with vehicle-treated samples (P < 0.05). In Experiment 3, semen treatment with both 100 µM D-ala GnRH-II and 10 µM SB-75 partially rescued sperm motility and morphology measures. These data suggest that GnRH-II and its receptor regulate porcine sperm function in an autocrine/paracrine manner.
Zebra finches (Taeniopygia castanotis) display varying degrees of stress resilience in response to constant light.
Pham K, Lazenby M, Yamada K … +2 more , Lattin CR, Wada H
Gen Comp Endocrinol · 2025 Jan · PMID 39592083 · Full text
The ability for traits to recover after exposure to stress varies depending on the magnitude, duration, or type of stressor. One such stressor is circadian rhythm disruption stemming from exposure to light at night. Circ...
The ability for traits to recover after exposure to stress varies depending on the magnitude, duration, or type of stressor. One such stressor is circadian rhythm disruption stemming from exposure to light at night. Circadian rhythm disruption may lead to long-term physiological consequences; however, the capacity in which individuals recover and display stress resilience is not known. Here, we exposed zebra finches (Taeniopygia castanotis) to constant light (24L:0D) or a regular light/dark cycle (14L:10D) for 23 days, followed by a recovery period for 12 days. We measured body mass, corticosterone, and glucose levels at multiple timepoints, and relative protein expression of glucocorticoid receptors at euthanasia. Body mass significantly increased over time in light-exposed birds compared to controls, but a 12-day recovery period reversed this increase. Baseline levels of circulating glucose decreased in light-exposed birds compared to controls, but returned to pretreatment levels after the 12-day recovery period. In contrast, the glucose stress response did not show a similar recovery trend, suggesting longer recovery is needed or that this is a persistent effect in light-exposed birds. Surprisingly, we did not detect any differences in baseline corticosterone or reactivity of the hypothalamic-pituitiary-adrenal (HPA) axis between groups throughout the experiment. Moreover, we did not detect differences between relative protein expression of glucocorticoid receptors or a relationship with HPA axis reactivity. Yet, we found a positive relationship between glucocorticoid receptors and the glucose stress response, but only in the light group. Our results indicate that physiological and morphological traits differ in their ability to recover in response to constant light and warrants further investigation on the mechanisms driving stress resilience under a disrupted circadian rhythm.
Complementary and additive functions of TRα and TRβ during intestinal remodeling as revealed by ChIP-Seq analysis on wild type and TR knockout animals.
Tanizaki Y, Zhang H, Shi YB
Gen Comp Endocrinol · 2025 Jan · PMID 39592082 · Full text
Intestinal structure is drastically changed from fetal to adult form during postembryonic development, a period around birth in mammals. This process is regulated by thyroid hormone (T3) via its receptors, T3 receptor (T...
Intestinal structure is drastically changed from fetal to adult form during postembryonic development, a period around birth in mammals. This process is regulated by thyroid hormone (T3) via its receptors, T3 receptor (TR) α and TRβ during anuran metamorphosis. Here, we used intestinal remodeling during Xenopus tropicalis metamorphosis, which serves as a model for human postembryonic development, to identify TR-bound genes and determine the relative contribution to target gene binding by TRα and TRβ. We first examined the localization of TRα and TRβ mRNA during metamorphosis in Xenopus tropicalis and found that TRα was broadly expressed in the intestinal tissues from premetamorphosis to the end of metamorphosis, while TRβ was expressed at low levels during premetamorphosis but was upregulated at the climax of metamorphosis when intestinal stem cells are formed and proliferate. Interestingly, both TR genes were co-expressed in different cell types, including stem cells. Chromatin immunoprecipitation (ChIP)-seq analyses of the intestine from wild type, TRα- or TRβ-knockout premetamorphic tadpoles treated with or without T3 for 18 h identified many TR-bound genes and revealed the effects of individual TR knockout on the binding of target genes by TR. We found that individual TR knockout reduced both the number of TR-bound genes and the extent of TR binding to target genes with TRα knockout had a much more dramatic effect than TRβ knockout. On the other hand, the TR-bound genes were largely common among the three genotypes. These findings suggest that both TRα and TRβ contribute to target binding with TRα having a bigger contribution in premetamorphic intestine.
Estradiol affects the expression of essential molecular factors involved in luteinizing hormone secretion in the plains vizcacha.
Proietto S, Cortasa SA, Schmidt AR … +7 more , Corso MC, Inserra PIF, Di Giorgio NP, Lux-Lantos V, Vitullo AD, Halperin J, Dorfman VB
Gen Comp Endocrinol · 2025 Jan · PMID 39551248 · Publisher ↗
The plains vizcacha is a rodent that shows reactivation of the hypothalamic-pituitary-ovary (HPO) axis activity at mid-gestation. This process is enabled by the secretion of hypothalamic gonadotropin-releasing hormone (G...
The plains vizcacha is a rodent that shows reactivation of the hypothalamic-pituitary-ovary (HPO) axis activity at mid-gestation. This process is enabled by the secretion of hypothalamic gonadotropin-releasing hormone (GnRH) at mid-gestation, followed by follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion. However, a decrease in the pituitary GnRH receptor (GnRHR) expression is concomitantly determined. Moreover, an increment in the pituitary expression of estrogen receptor alpha (ERα) has been determined. This work aimed to study the impact of estradiol (E2) on GnRHR expression, the transcription factors early growth response protein-1 (Egr-1) and steroidogenic factor-1 (Sf-1), as well as on LH secretion. Three experimental approaches were performed: a physiological one with pregnant plains vizcachas, an in vivo approach with ovariectomized (OVX) animals treated with E2 (OVX + E2), and an ex vivo approach using pituitary glands exposed to a combination of GnRH and E2. Significant increased pituitary expression of Sf-1 and Egr-1 was determined at mid-gestation. Ovariectomy significantly increased adenohypophyseal expression levels of GnRHR, Egr-1, and Sf-1, as well as LH secretion. Then, OVX + E2 showed similar levels to SHAM. Adenohypophyses exposed to GnRH showed induced GnRHR, Egr-1, and Sf-1 expression, and LH secretion, while GnRH + E2 reverted these changes. The mid-gestation pituitary GnRHR decrease may result from the combination of increased E2 and GnRH secretion. Nevertheless, the increased expression of Egr-1 and Sf-1 at mid-gestation, together with LH release, suggests the tightly and complex regulatory system that takes place at mid-gestation, enabling a new progesterone surge that successfully carries the pregnancy to term. NEW & NOTEWORTHY: A significant increment of Sf-1 and Egr-1 at the pituitary of mid-gestating plains vizcachas was determined. Moreover, E2 reverted GnRHR, Egr-1, Sf-1, and LH increase in ovariectomized vizcachas' pituitaries and ex vivo pituitaries exposed to GnRH. The decrease of the pituitary GnRHR at mid-gestation may result from the increased E2 and GnRH levels. A tightly and complex regulatory system may take place at mid-gestation enabling a new surge of progesterone that carries pregnancy to term.
Stress Axis: Molecular and Cellular Regulation of the HPI/HPA Axis.
Gen Comp Endocrinol · 2025 Jan · PMID 39551247 · Publisher ↗
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Spatial and quantitative gene expression analysis of SREB receptors in the gonads of green-spotted pufferfish (Dichotomyctere nigroviridis).
Breton TS, Oliveira ME, Chillemi T … +7 more , Harriman W, Korasadowicz J, Saverese E, Bourget E, Murray CA, Martyniuk CJ, DiMaggio MA
Gen Comp Endocrinol · 2025 Jan · PMID 39536984 · Full text
Super-conserved Receptors Expressed in Brain (SREB) are a highly conserved family of orphan G protein-coupled receptors that consist of three members in most vertebrates: SREB1 (GPR27), SREB2 (GPR85), and SREB3 (GPR173)....
Super-conserved Receptors Expressed in Brain (SREB) are a highly conserved family of orphan G protein-coupled receptors that consist of three members in most vertebrates: SREB1 (GPR27), SREB2 (GPR85), and SREB3 (GPR173). Each receptor is associated with diverse physiological processes and expressed in both ovaries and testes, but reproductive functions are only beginning to be understood. In addition, some fishes gained a novel fourth gene, SREB3B, which may have unique functions. The purpose of this study was to conduct a spatial and quantitative analysis of SREBs in the gonads of pufferfish (Dichotomyctere nigroviridis), which expresses all four genes. Multiplex RNAscope and absolute qPCR were used to assess gene expression patterns in both ovaries and testes. Expression was detected in early ovaries and dominated by sreb1 (approximately 2500 copies/ng RNA vs. 300 or less for others), with notable expression of all receptors in primary oocytes, granulosa cells, and small numbers of extra-follicular cells. Within primary oocytes, sreb1 and sreb3b exhibited diffuse patterns that may indicate early functions, while sreb2 and sreb3a were granular and may reflect stored mRNA. Early testicular development was dominated by sreb1 and sreb2 (∼5000 copies/ng RNA) in spermatogonia. These patterns were somewhat reduced in late testes (∼1000-2600 copies/ng RNA), but sreb3b exhibited a novel spatial pattern (∼380 copies/ng RNA) within spermatogenic cysts. These results highlight diverse roles for the SREB family, and sreb3b is hypothesized to have unique roles in fish reproduction.
Identification and functional analysis of six melanocortin-4-receptor-like (MC4R-like) mutations in goldfish (Carassius auratus).
Wang Y, Yang T, Mo H … +7 more , Yao M, Song Q, Yu H, Du Y, Li Y, Yu J, Wang L
Gen Comp Endocrinol · 2025 Jan · PMID 39536983 · Publisher ↗
Melanocortin receptor-4 (MC4R) belongs to the G protein-coupled receptor family, characterized by a classical structure of seven transmembrane domains (7TMD). They play an important role in food intake and weight regulat...
Melanocortin receptor-4 (MC4R) belongs to the G protein-coupled receptor family, characterized by a classical structure of seven transmembrane domains (7TMD). They play an important role in food intake and weight regulation. In the present study, we identified melanocortin-4-receptor-like (caMC4RL) mutants of goldfish from the Qian River in the Qin Ling region and characterized their functional properties, including the constitutive activities of the mutants, ligand-induced cAMP and ERK1/2 accumulation, and AMPK activation. The results show that six caMC4RL mutants were identified in goldfish from the Qian River in the Qin Ling region, and are located in the conserved position of the Cyprinidae MC4Rs. The mutations (E57K, P296S, and R302T/K) result in the loss of Gs signaling function. The mutations (P296 and R302T/K) exhibited biased signaling in response to ACTH stimulation in the MAPK/ERK pathway. In addition, the E57K mutant may play a role in weight regulation and could serve as molecular markers for molecular breeding. These data will provide fundamental information for functional studies of teleost GPCR mutants and MC4R isoforms.
Thyroid hormones activate TH/E receptor/regulator system and drive Na/K-ATPase in the ovarian wall of hypothyroid air-breathing fish (Anabas testudineus Bloch).
Viswanath M, Peter MCS
Gen Comp Endocrinol · 2025 Jan · PMID 39536982 · Publisher ↗
In fish, as in other vertebrates, thyroid hormones (THs) act on many biological processes including growth and reproduction. Primary THs such as thyroxine (T) and triiodothyronine (T) are known for their direct action on...
In fish, as in other vertebrates, thyroid hormones (THs) act on many biological processes including growth and reproduction. Primary THs such as thyroxine (T) and triiodothyronine (T) are known for their direct action on osmoregulatory organs regulating ion osmotic homeostasis in many teleost fishes. However, it is unclear how these hormones interact with estradiol-17β (E), an ovarian hormone that regulates the development of oocytes. We thus examined the short-term in vivo action of varied THs such as T T and T, a potent TH metabolite diiodothyronine, on the expression pattern of receptors of THs and E in the ovarian wall of the hypothyroid climbing perch to identify the interactive pattern of TH/E receptor system and the molecular dynamics of Na/K-ATPase (NKA) subunits in the ovarian wall that provides structural and functional support to ovary. We found differential pattern of transcript abundance of NKA subunits isoforms such as nkaα1a, nkaα1b, nkaα1c atp1b1, atp1b2 and fxyd3, fxyd5, fxyd6, TH receptor isoforms (tr<, trβ, tr<B), deiodinases (deo1, deo2 and deo3) and TH transporter (mct8, mct10) and E receptor (er<, erβ, gper), aromatases (cyp19a1a, cyp19a1b) and steroidogenic enzymes (17β-hsd, sf-1, star) in ovarian wall in response to T, T and T administration in MMI-treated fish. The transcript abundance pattern provides evidence for a direct role of THs in the ovarian wall of hypothyroid fish. It confirms a targeted interaction of THs with ER/cyp19a1 and NKA systems. Pattern analysis further revealed that T could produce maximum activation of the TR/Deo/Mct and ER/cyp19a1 systems among three iodinated tyrosines, bringing synergistic interaction between the TH and E systems in the ovarian wall. This novel evidence of direct interaction between the TH/E system and the NKA system in the ovarian wall further testifies to an ion osmotic role for THs in this ovarian structure.
Differential activation of six galanin receptors by the spexin peptide in yellowtail kingfish (Seriola lalandi).
Wang B, Tian Z, Yu Z … +4 more , Cui A, Jiang Y, Huang H, Xu Y
Gen Comp Endocrinol · 2024 Dec · PMID 39426688 · Publisher ↗
Spexin (SPX1) is a novel neuropeptide composed of 14 amino acids and well conserved across vertebrates, and it has been implicated in various physiological functions via galanin receptor 2 (GALR2) and GALR3. However, the...
Spexin (SPX1) is a novel neuropeptide composed of 14 amino acids and well conserved across vertebrates, and it has been implicated in various physiological functions via galanin receptor 2 (GALR2) and GALR3. However, the detailed signaling pathways mediating its actions in target cells are still largely unknown. Accordingly, we addressed this issue in the present study using yellowtail kingfish as a model. SPX1 significantly increased CRE-luc activity in COS-7 cells expressing its cognate receptors GALR2a and GALR2b, and this stimulatory effect was attenuated by two inhibitors of the PKA pathway. Similarly, an evident induction of SRE-luc activity was observed when COS-7 cells transfected with GALR1b, GALR2a, GALR2b, GALR type 1, or GALR type 2 were challenged with SPX1, and two blockers of the PKC pathway suppressed this stimulatory action. Moreover, SPX1 markedly elevated NFAT-RE-luc activity in COS-7 cells expressing GALR1a, GALR2a, or GALR2b, and this promotion was inhibited by two antagonists of the Ca route. Overall, our results have revealed that activation of six yellowtail kingfish galanin receptors by the SPX1 peptide may occur with different downstream signaling events, which could account for its pleotropic functions.
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