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Gen. Comp. Endocrinol. [JOURNAL]

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Intelectin-1 promotes granulosa cells proliferation and modulates apoptosis via ERK1/2, AKT, and insulin receptor signaling pathways in Large White and Meishan pigs.

Pich K, Respekta-Długosz N, Kurowska P … +4 more , Opydo M, Smolińska N, Dupont J, Rak A

Gen Comp Endocrinol · 2025 May · PMID 40250633 · Publisher ↗

Maintaining the proper balance between granulosa cells (Gc) proliferation and apoptosis is crucial for folliculogenesis and female fertility. Our previous study showed expression of omentin-1 (intelectin-1, ITLN1) in the... Maintaining the proper balance between granulosa cells (Gc) proliferation and apoptosis is crucial for folliculogenesis and female fertility. Our previous study showed expression of omentin-1 (intelectin-1, ITLN1) in the porcine ovarian follicles; however, its impact on Gc functions remains unknown. Therefore, this study aimed to determine the in vitro effects of ITLN1 on Gc proliferation and apoptosis in Large White (LW) and Meishan (MS) pigs. These breeds were chosen due to their distinct reproductive characteristics: MS pigs are known for maintaining a higher number of follicles during the follicular phase and exhibiting greater estradiol synthesis compared to LW pigs. Porcine Gc were incubated with ITLN1 (10-100 ng/mL) for 24-72 h, and the viability/proliferation (alamarBlue/BrdU assays), cell cycle progression (flow cytometry) and the gene and protein expression of proliferation/apoptotic markers (PCNA, cyclins A1, B2, D1, E1, caspases-3, -9, BCL-2, BAX, FAS, FADD, XIAP) (real-time PCR, western blotting) were assessed. Next, the effect of ITLN1 on the phosphorylation of several kinases (AKT, AMPK, ERK1/2, STAT3, PKA) and the gene and protein expression of the insulin receptor (INSR) were studied (real-time PCR, western blotting). Then, using pharmacological inhibitors of ERK1/2 (PD98059, 5 μM), AKT (LY294002, 10 μM) and INSR (1 μM), treated alone or with ITLN1 (S961, 50 ng/mL), we analyzed its involvement in the effects of ITLN1 on Gc proliferation/apoptosis. We demonstrated that ITLN1 had a mitogenic effect on Gc by enhancing cell cycle progression and modulating the levels of PCNA, cyclins and apoptotic factors via ERK1/2, AKT, and INSR, suggesting that ITLN1 is a newly identified regulator in ovarian folliculogenesis, regardless of the fatness degree of pigs.

Endocrine regulation of feeding in non-transgenic and transgenic fluorescent orange tiger barb (Puntigrus tetrazona).

Lindstrom A, Volkoff H

Gen Comp Endocrinol · 2025 May · PMID 40228648 · Publisher ↗

Tiger barbs are popular tropical aquarium fish but despite their economic importance, nothing is known about their feeding physiology, in particular their endocrine regulation of feeding. The tiger barb has also been use... Tiger barbs are popular tropical aquarium fish but despite their economic importance, nothing is known about their feeding physiology, in particular their endocrine regulation of feeding. The tiger barb has also been used to make genetically modified fluorescent fish but the influence of this genetic modification on their physiology is poorly understood. In this study, we submitted both non-transgenic (NT) and transgenic fluorescent orange (T) fish to 2 weeks of fasting or different temperatures (20, 25 and 30 °C) and assessed food intake and the expression of appetite regulators in brain, intestine and liver. Fasting had no effect on appetite regulators in the intestine, and decreased liver leptin expression in NT fish only. Fasting caused an overall increase and decrease in brain orexigenic and anorexigenic factors, respectively. The nature of peptides affected by this response differed between strains (MCH, ghrelin, POMCb in both NT and T, orexin in NT only, CRF and CCK in T only). In both T and NT fish, increasing temperatures increased food intake. Temperature affected the expression of most of the peptides examined, but the effects differed between the two fish strains. A shift from 25 to 20 °C increased hepatic leptin in NT and T, and intestine ghrelin in NT and had no effect on brain expression. A shift from 25 to 30 °C did not affect intestine or liver expressions, increased orexin, MCH and CRF brain expression in NT and T, and increased POMCb and CCKa expressions in T. Our study presents new information on the endocrine regulation of feeding in tiger barb, and provides insights on how transgenesis might affect feeding physiology of fish.

Using transcriptome analysis to investigate the induction of vitellogenesis in female Japanese eels (Anguilla japonica).

Zuo C, Zhang Y, Zhang X … +8 more , Liu J, Lyu L, Ma T, Chen L, Yu W, Li Y, Wen H, Qi X

Gen Comp Endocrinol · 2025 May · PMID 40228647 · Publisher ↗

Oogenesis, encompassing folliculogenesis, development, and maturation, is a complex physiological process that is not solely regulated by gonadotropins but is also actively influenced by multiple growth factors produced... Oogenesis, encompassing folliculogenesis, development, and maturation, is a complex physiological process that is not solely regulated by gonadotropins but is also actively influenced by multiple growth factors produced by the oocyte and its surrounding follicular cells. The Japanese eel (Anguilla japonica) has a complex life history, resulting in many uncertainties regarding its growth, development, and reproduction. Under artificial culture conditions, oocyte development in the Japanese eel is arrested and can only progress to the vitellogenic stage through artificial induction. In the present study, we observed that, despite receiving the same hormone treatment as normally developing individuals, a small proportion of female eels exhibited oocytes arrested at the perinucleolar stage. Transcriptome analysis revealed that differentially expressed genes are involved in multiple reproductive-related physiological processes and functional pathways, such as tachykinin system, MAPK signaling pathway, steroid-related pathways, oocyte meiosis, Wnt signaling pathway and GnRH signaling pathway. The abnormal expression of the two follicle-stimulating hormone (FSH) subunit genes may be a key factor contributing to this phenomenon. This study reveals the underlying causes of ovarian developmental arrest in hormonally induced female Japanese eels from the perspective of the brain-pituitary-gonad (BPG) axis, providing a research foundation for the artificial reproduction of Japanese eels.

Molecular identification and reproductive function of spexin in the big-belly seahorse (Hippocampus abdominalis).

Zhao L, Li Y, Li J … +3 more , Jin W, Chen J, Wang B

Gen Comp Endocrinol · 2025 May · PMID 40199389 · Publisher ↗

Limited data are available regarding reproductive endocrinology of seahorse. Here, we reported the potential function of spexin (SPX1) in the reproduction of seahorse. SPX1, also known as neuropeptide Q (NPQ), is a novel... Limited data are available regarding reproductive endocrinology of seahorse. Here, we reported the potential function of spexin (SPX1) in the reproduction of seahorse. SPX1, also known as neuropeptide Q (NPQ), is a novel neuropeptide that coevolved with galanin and kisspeptin. In the current study, the entire open reading frame (ORF) sequence of spx1 of the big-belly seahorse (Hippocampus abdominalis) was cloned and characterized, which is 360 base pairs in length, encoding a 119-amino acid precursor peptide, with a 26-aa signaling peptide and a 14-aa C-terminal amidated mature peptide. Tissue distribution expression profiles of spx1 transcripts were analyzed and revealed that spx1 mRNA could be detected in a variety of tissues, with the highest abundance in the mixture tissues of brain and pituitary. The expression profile of spx1 mRNA in the mixture of brain and pituitary during the first reproductive cycle of the big-belly seahorse was evaluated, which showed that the expression level of spx1 mRNA was highest during the critical period of ovarian and testicular transition from stage II to stage III at 3.5-month old, and high in females with IV-stage, V-stage and VI-stage, as well as in males with the early-stage brood pouch, suggesting that SPX1 may play a crucial role at these stages of gonadal and brood pouch development. Intraperitoneal injection of SPX1 can suppress the mRNA expressions of galr2b and fshβ in female seahorses, however, it promoted the mRNA expressions of spx1, gal, kiss2, gnrh2, kiss2r, galr1a, galr2b, gnrh3 and gnihr in males, besides, low doses of SPX1 enhanced lhβ mRNA expression, while high dose of SPX1 suppressed it. Intraperitoneal injection of SPX1 did not alter the mRNA levels of spx1, gal, kiss2, galr1a, galr2a, gnihr or plasma 17β-E2 in females, nor did it change the mRNA levels of galr2a, gthα, fshβ or plasma 11-KT in males. These results revealed that SPX1 may participate in regulating reproduction of the big-belly seahorse by controlling production of GnRH2, GnRH3, FSH and LH of HPG axis, as well as some key hypothalamic neuropeptides including Kiss and GAL. Above all, our results indicate the presence of a functional SPX1 system in the big-belly seahorse, as well as reveal its potential significance in the neuroendocrine regulation of reproduction in this species, which also lay a foundation for future research on optimizing fish reproductive performance through the regulation of SPX1.

Urotensin II in GIFT Nile tilapia (Oreochromis niloticus): CDS cloning, tissue distribution, and in vitro regulation of male reproduction.

Bai Y, Zhang X, Yu X … +5 more , Lian Y, Lai K, Chen X, Li W, Sun C

Gen Comp Endocrinol · 2025 May · PMID 40180193 · Publisher ↗

The caudal neurosecretory system (CNSS), present in all jawed vertebrates, except sarcopterygians, is considered a major site of urotensin II (UII) secretion. UII, a 12-amino acid peptide with a conserved hexapeptide rin... The caudal neurosecretory system (CNSS), present in all jawed vertebrates, except sarcopterygians, is considered a major site of urotensin II (UII) secretion. UII, a 12-amino acid peptide with a conserved hexapeptide ring structure, is also secreted by other tissues and found in sarcopterygians. UII has been associated with endocrine regulation, osmoregulation, and several pathophysiological conditions. In this study, CDS of GIFT Nile tilapia (Oreochromis niloticus) UII (tUII) and its receptors UT1 (tUT1) and UT2 (tUT2) were cloned from the CNSS and cerebellum, respectively. Phylogenetic analysis indicated that tUII, tUT1, and tUT2 shared a high homology with the ones of cichlid species, Haplochromis burtoni and Neolamprologus brichardi. Despite variations in precursor peptide sequences, the core sequence of the mature UII peptide remains highly conserved. tUII was predominantly expressed in the CNSS, while tUT1 and tUT2 were widely distributed in the central nervous system (CNS) and peripheral tissues of male and female tilapia. Functional studies revealed that synthetic tUII significantly activated luciferase activity in HEK293T cells transiently transfected with pNFAT-TA-Luc vectors and tUT1 or tUT2. In vitro studies in male GIFT Nile tilapia showed that tUII stimulated mRNA expression of gnrh1, gnrh2, and gnrh3 in a dose-dependent manner by brain fragments, as well as fshβ, lhβ, and gthα by primary culture of pituitary cells. Furthermore, tUII promoted the expression of gnrhr1, gnrhr2, and gnrhr3 in pituitary cells and stimulated mRNA levels of fshr, lhr, arα, cyp11b2, and dmrt1 in testicular tissue. All these stimulatory effects of tUII on gene expression mentioned above were blocked by the non-selective UT antagonist urantide, suggesting for the first time that the actions of tUII were mediated via tUT1 or tUT2. In addition, tUII could significantly stimulate the secretion of testosterone by testis fragments. Taken together, these results suggest that tUII may play a role in reproductive regulation in male GIFT Nile tilapia.

Effect of stress on profiles of fecal glucocorticoid and androgen metabolites and antler status in marsh deer (Blastocerus dichotomus).

de Souza LJ, Dos Santos Zanetti E, Barbanti Duarte JM

Gen Comp Endocrinol · 2025 May · PMID 40180192 · Publisher ↗

The influence of glucocorticoids on reproductive hormones and antler cycles in cervids remains poorly understood, particularly in tropical species. Most Neotropical deer, like the marsh deer (Blastocerus dichotomus), lac... The influence of glucocorticoids on reproductive hormones and antler cycles in cervids remains poorly understood, particularly in tropical species. Most Neotropical deer, like the marsh deer (Blastocerus dichotomus), lack a defined breeding season or a clear link between antler stage and reproductive status. Furthermore, conflicting data regarding stress impacts on androgen levels and antler development underscore the need for further research. We evaluated the effects of stress on fecal glucocorticoid metabolites (FGMs), fecal androgen metabolites (FAMs) and antler status in captive marsh deer. Nineteen males underwent a quarantine after being transferred to a new breeding site, with antler status monitored weekly. Daily fecal samples from 17 individuals were analyzed using EIA to measure FAM and FGM concentrations. Among 12 animals with fully developed antlers, nearly 60 % (n = 7) experienced antler casting, an unusual synchrony for this species. A positive correlation was found between FAM and FGM levels (p < 0.001; r = 0.40). We compared FAM and FGM levels between juveniles and adults, as well as among the antler categories. Adults exhibited 1.2-fold higher FGM levels than juveniles, with no differences in FAM levels. Males with hard antlers showed the highest FAM levels, while FGM levels were highest in males with velvet antlers. We hypothesize that intense stress negatively affected antler retention, leading to antler casting. Our findings suggest that stressful stimuli may trigger adrenal secretion of glucocorticoids and androgens, providing insights into the relationship between stress and antler dynamics in marsh deer.

Global analysis of ligand-gated ion channel conservation across Platyhelminthes.

Caña-Bozada VH, Dawoud AAZ, Ramos-de la Cruz I … +4 more , Flores-Méndez LC, Barrera-Redondo J, Briones-Mendoza J, Yañez-Guerra LA

Gen Comp Endocrinol · 2025 Apr · PMID 40157577 · Publisher ↗

Ligand-gated ion channels (LGICs) are critical for neurotransmission, mediating responses to neurotransmitters and hormones, and influencing diverse physiological processes. This study identifies and classifies LGICs acr... Ligand-gated ion channels (LGICs) are critical for neurotransmission, mediating responses to neurotransmitters and hormones, and influencing diverse physiological processes. This study identifies and classifies LGICs across Platyhelminthes, with a particular focus on parasitic neodermatans, which impact human and animal health. Using bioinformatics tools, we analyzed LGICs from 41 neodermatan species and expanded our investigation to encompass vertebrates, other invertebrates, and non-bilaterians to trace LGIC evolutionary pathways across Metazoa. We identified 2,269 putative LGICs within neodermatan species, which we classified into the cys-loop, ASIC/Deg/ENaC, iGluR, and P2X families. Our phylogenetic and clustering analyses reveal lineage-specific patterns with distinct evolutionary trajectories for each LGIC family in neodermatans compared to free-living platyhelminths and other taxa. Notably, the ASIC/Deg/ENaC family displayed the greatest degree of neodermatan-specific divergence, while cys-loop and P2X families were more conserved across taxa. To provide insight into their potential physiological roles, we analyzed LGIC expression patterns in Schistosoma mansoni, revealing widespread expression across neuronal and muscle cell types. The distribution of acid-sensing ion channels (ASICs) in both neurons and muscles suggests a role in neuromuscular signalling, while the P2X receptor (Smp_333600) exhibited sex-specific expression, potentially indicating distinct functional roles in males and females. Additionally, several cys-loop acetylcholine and GABA receptors showed differential neuronal and muscle expression, highlighting their likely contributions to cholinergic and inhibitory neurotransmission. These findings underscore the relevance of LGICs in parasite physiology, particularly in neuromuscular and sensory processes, and suggest potential targets for antiparasitic interventions.

Identification and expression of nuclear receptor genes during nutritive phagocyte development in sea urchin Mesocentrotus nudus gonads.

Ura K, Tsue S, Sato T … +7 more , Hagihara S, Satoh M, Higuchi I, Wang H, Nishimiya O, Ijiri S, Takagi Y

Gen Comp Endocrinol · 2025 Apr · PMID 40139329 · Publisher ↗

The role of the endocrine system during synthesis of the nutrients (e.g., proteins, lipids, polysaccharides) in the gonad in sea urchins is imperfectly understood. We identify genes encoding nuclear receptors (NRs) invol... The role of the endocrine system during synthesis of the nutrients (e.g., proteins, lipids, polysaccharides) in the gonad in sea urchins is imperfectly understood. We identify genes encoding nuclear receptors (NRs) involved in the development of nutritive phagocytes of the sea urchin Mesocentrotus nudus, and investigate their gene expression patterns during this time. RNA-seq analysis was performed on immature gonads using a next-generation sequencer. A total of 7,651,421 quality-controlled reads obtained using an Ion PGM sequencer were assembled into 175,092 contigs. BLASTn analysis identified 20 NR genes potentially involved in the development of nutritive phagocytes. Expression analyses revealed levels of four NR genes to increase during the development of nutritive phagocytes. These results indicate that these 20 NR genes have physiological functions in gonadal growth, and that 4 NR genes mainly control the expression of genes involved in the synthesis and metabolism of proteins, lipids, and polysaccharides during cellular proliferation in sea urchin gonads.

Light/darkness modulation of the hypothalamic-pituitary-ovarian axis in the plains vizcacha, Lagostomus maximus, a seasonal breeding species.

Charif SE, Inserra PIF, Villarreal FM … +9 more , Schmidt AR, Cortasa SA, Proietto S, Corso MC, Llanos Dumont MI, Di Giorgio NP, Halperin J, Vitullo AD, Dorfman VB

Gen Comp Endocrinol · 2025 Apr · PMID 40139328 · Publisher ↗

Photoperiod is the main environmental signal that affects animal behavior and reproduction. Light stimulus is traduced by a neural pathway that modulates pineal gland melatonin release, which synchronizes physiologic fun... Photoperiod is the main environmental signal that affects animal behavior and reproduction. Light stimulus is traduced by a neural pathway that modulates pineal gland melatonin release, which synchronizes physiologic functions with day duration, highly influencing seasonal reproduction. The plains vizcacha (Lagostomus maximus) is a Hystricomorph rodent with seasonal reproduction that inhabits the Neotropic in South America. The aim of this work was to elucidate the effect of light/darkness exposition on the reproductive hypothalamic-pituitary-ovarian (HPO) axis in the female plains vizcacha. During 15 days, animals were subjected to different light/darkness regimens (Control group, CTL: 12:12 h dark:light; Darkness group, DARK: continuous darkness; Light group, LIGHT: continuous light). The melatoninergic system and reproductive hormones were evaluated. Plasma melatonin levels significantly decreased in DARK whereas both melatonin receptors (MT and MT) expression significantly increased in the hypothalamus and decreased in the pituitary gland, and only MT expression increased in the ovaries. Continuous light did not induce significant variations in melatonin levels related to CTL, however, MTs expression changed at pituitary and ovary levels. Strikingly, both light/darkness regimens increased reproductive hormone expression. While darkness induced hypothalamic gonadotropin-releasing hormone (GnRH) expression and estradiol (E) secretion, light increased LH and progesterone (P) secretion. In conclusion, light availability may impact the reproductive axis of plains vizcacha inducing hormonal changes, with an organ-specific response, and sustaining HPO axis activity, thus ensuring reproduction. Environmental light and darkness, their availability and exposure length, could synchronize the reproductive axis in seasonal breeding species like the plains vizcacha. New & Noteworthy: Hypothalamic, pituitary, and ovarian variations were induced by continuous light or darkness in the plains vizcacha. Plasma melatonin decreased by continuous darkness-inducing hypothalamic, pituitary, and ovarian melatonin receptors variations. Fifteen days of continuous darkness induced GnRH, LH, and estradiol secretion, while 15 days of continuous light induced LH and P secretion. Environmental light/darkness would synchronize the reproductive axis in seasonal breeding species like the plains vizcacha.

Coordinated regulation of the hypothalamic-pituitary-somatotropic axis in Chinese sea bass (Lateolabrax maculatus) under temperature and salinity changes.

Zhou T, Li J, Chen J … +3 more , Lu W, Zhang L, Cheng J

Gen Comp Endocrinol · 2025 Apr · PMID 40139327 · Publisher ↗

Hypothalamic-Pituitary-Somatotropic (HPS) axis contains essential endocrine factors and plays diverse roles in the growth of teleost living in dynamic aquatic environments. In this study, 43 HPS axis genes were character... Hypothalamic-Pituitary-Somatotropic (HPS) axis contains essential endocrine factors and plays diverse roles in the growth of teleost living in dynamic aquatic environments. In this study, 43 HPS axis genes were characterized in Chinese sea bass (Lateolabrax maculatus), the economically important marine fish highly adaptable to a wide range of temperatures and salinities. The phylogeny, conserved domain, molecular evolution and expression of L. maculatus HPS axis genes revealed their evolutionary conservation, with examples of functional divergence in duplication-originated genes (sst1a/1b, igf1ra/1rb). Weighted gene co-expression network analysis (WGCNA) among L. maculatus tissues revealed strong co-expression of HPS genes (ssts, igf1rs, igfbps) in brains than in livers and muscles, interacting with feeding (cartpt, negr1), metabolism (grik3, drd4), and growth (apba1) functional genes. Under temperature changes, L. maculatus HPS genes were more actively regulated in brains than in livers and muscles, with the hypothalamic and pituitary HPS genes mainly regulated in brains, whereas the peripheral HPS genes were regulated in livers and muscles. WGCNA revealed that HPS axis mainly interacted with stress and feeding activity in brains of L. maculatus under temperature stress, while it interacted with metabolism and growth activity in livers and muscles. Similar co-expression of HPS genes (sstrs, igf1rbs, igfbps) were with feeding (pik3r4), metabolism (mrps, ndufa12) and growth (sulf2, peli3, apod) functions in brains, indicating that HPS axis could regulate growth through coordinated mediation of the food-intake and energy metabolism in L. maculatus under environmental stress. Our results provided comprehensive understanding about the L. maculatus HPS axis responding to environmental stimuli, which are crucial for the growth regulation and will provide important insights into fast-growing L. maculatus cultivation.

Identification and characterization of neuropeptides in sea urchin Strongylocentrotus intermedius.

Li Q, Zhang M, Liu K … +5 more , Yuan M, Wang W, Xu D, Tian D, Wang X

Gen Comp Endocrinol · 2025 Apr · PMID 40127741 · Publisher ↗

Neuropeptides play essential roles in regulation of feeding, reproduction and behavior in echinoderms. But the neuropeptide function has not been explored extensively in sea urchins. The tube feet contain part of the per... Neuropeptides play essential roles in regulation of feeding, reproduction and behavior in echinoderms. But the neuropeptide function has not been explored extensively in sea urchins. The tube feet contain part of the peripheral nervous system in echinoids, comprising both neurosensory and neuromuscular components. In this study, we sequenced transcriptome of Strongylocentrotus intermedius tube feet and identified 26 neuropeptide precursor transcripts, including ANpeptide, bursicons, calcitonin, corazonin, gonadotropin-releasing hormone (GnRH), glycoprotein-type hormones (GPA & GPB), insulin-related peptides (dilp7 & octinsulin), luqin, NGFFFamide, prolactin-releasing peptide/short neuropeptide F (PrRP/sNPF), orexin, pedal peptides, SALMFamides, somatostatin/allatostatin-C (SS1 & SS2), thyrotropin-releasing hormone (TRH), and vasopressin-oxytocin. In addition, we further compared the expression levels of neuropeptide precursors between red and white tube feet, and found 3 neuropeptides (bursicon β, octinsulin and luqin) had higher expression in red tube feet, potentially related to pigmentation or other pigment-related functions. We also observed ultrastructure of tube feet by transmission electron microscopy (TEM) and found large amount of muscle fibers, nerve plexus and vesicles in tube feet. Neuropeptides might play roles in these structures of tube feet. Our study represents the first identification of neuropeptides in tube feet of S. intermedius, and will contribute to a complete understanding on the roles of various neuropeptides in sea urchin echinoderms.

Temperature modulates 17β-estradiol regulation of oogenesis protein expression in the liver of the eurythermal pupfish Cyprinodon nevadensis.

Lema SC, Krayeva KA, Dale ZA … +1 more , Guerre TE

Gen Comp Endocrinol · 2025 Apr · PMID 40101872 · Publisher ↗

Female fish experiencing atypically high or prolonged elevations in temperature during oogenesis can suffer impaired oocyte development with fewer or smaller eggs, eggs with reduced yolk content or thinner envelopes, and... Female fish experiencing atypically high or prolonged elevations in temperature during oogenesis can suffer impaired oocyte development with fewer or smaller eggs, eggs with reduced yolk content or thinner envelopes, and lower egg viability. These changes in oocyte quality and quantity are in part caused by diminished liver synthesis of egg yolk (vitellogenin, Vtg) and egg envelope (choriogenin) proteins at anomalously high temperatures. Those declines in liver Vtg and choriogenin production are commonly paralleled by reduced blood concentrations of 17β-estradiol (E). However, it is unclear whether declines in liver vitellogenin and choriogenin production at elevated temperatures result solely from lower circulating E or if other aspects of E signaling are also altered to diminish liver synthesis of oogenesis proteins. In this study, adult female Amargosa River pupfish (Cyprinodon nevadensis amargosae), a species with asynchronous follicular development, were maintained at 20 °C, 28 °C, or 36 °C and then administered E or vehicle solution. Ovarian gonadosomatic index (GSI) values and plasma E were lower in females at 36 °C compared to those at cooler temperatures. Females at 36 °C also had reduced plasma Vtg protein, lower liver abundances for mRNAs encoding vitellogenin genes (vtgAa, vtgAb, vtgc), choriogenin genes (cgh, cghm, cgl), and estrogen receptor α (esr1). Supplemental E increased plasma E in females at all temperatures, but only upregulated liver vitellogenin and choriogenin mRNAs at 36 °C, despite E upregulation of hepatic esr1 receptor transcripts at all temperatures. Females at 36 °C also exhibited higher liver mRNA abundances for sex hormone-binding globulin (shbg) and cytochrome P450 family 1 subfamily A member 1 (cyp1a1), an estrogen-metabolizing monooxygenase enzyme that converts E to 2-hydroxyestradiol. Together, these findings indicate elevated temperatures diminish E stimulation of liver Vtg and choriogenin expression in pupfish via effects on several aspects of E signaling including circulating E concentrations and liver esr1 expression as well as shbg and cyp1a1 expression, which may result in changes to free:bound E and the rate of hepatic E inactivation. These results also demonstrate that E replacement can help compensate for high temperature-induced declines in hepatic oogenesis gene expression in female pupfish.

Post-lactation mass recovery and metabolic hormone dynamics in adult female Weddell seals.

Kirkham AL, Avery JP, Beltran RS … +1 more , Burns JM

Gen Comp Endocrinol · 2025 Apr · PMID 40074089 · Full text

Weddell seal (Leptonychotes weddellii) females lose substantial body mass across an intensive, nutritionally restricted lactation period and then must rapidly recover mass during the short Antarctic summer. In this study... Weddell seal (Leptonychotes weddellii) females lose substantial body mass across an intensive, nutritionally restricted lactation period and then must rapidly recover mass during the short Antarctic summer. In this study, we examined endocrine dynamics associated with mass loss across lactation and subsequent realimentation in Weddell seals, comparing patterns between seals that recently gave birth and demographically similar non-reproductive females (skip females) in McMurdo Sound, Antarctica. Postpartum seals near weaning (∼35 days postpartum, n = 64) and skip females (n = 32) were handled during early austral summer (November/December) and rehandled in late summer (January/February). Body mass, body composition (% lipid), and a suite of metabolic hormones (growth hormone (GH), insulin-like growth factor (IGF)-I, cortisol, total thyroxine (tT), free thyroxine (fT), and total triiodothyronine (tT) and IGF binding protein (IGFBP)-2 and -3) were measured. Postpartum seals gained mass after weaning (0.98 ± 0.56 kg·day (mean ± SD)), primarily as lean tissue rather than lipid, while their serum concentrations of tT and fT, IGF-I, and cortisol increased. Their circulating GH and IGFBP-2 concentrations decreased and correlated negatively with mass. Skip females had greater body masses and lipid stores than postpartum seals at the end of the lactation period in early summer, but they lost mass (-1.03 ± 0.35 kg·day) and lipid stores over summer while their serum cortisol concentrations increased. Overall, body mass and composition of postpartum and skip females converged across summer. This convergence, likely driven in large part by contrasting endocrine profiles between the groups, may allow female Weddell seals to reach an advantageous seasonal body mass "set point" by onset of winter.

Three types of 17β-hydroxysteroid dehydrogenases involved in Japanese eel ovarian steroidogenesis.

Suzuki H, Ito R, Ozaki Y … +1 more , Kazeto Y

Gen Comp Endocrinol · 2025 Apr · PMID 40024447 · Publisher ↗

The synthesis of estradiol-17β (E2), an important steroid hormone in piscine gametogenesis, is catalyzed by various steroidogenic enzymes under the control of pituitary gonadotropins (Gths), follicle-stimulating hormone... The synthesis of estradiol-17β (E2), an important steroid hormone in piscine gametogenesis, is catalyzed by various steroidogenic enzymes under the control of pituitary gonadotropins (Gths), follicle-stimulating hormone (Fsh), and luteinizing hormone (Lh). Among these enzymes, 17β-hydroxysteroid dehydrogenases (Hsd17bs) with 17β-hydroxysteroid dehydrogenase/17-ketosteroid reductase activities are crucial enzymes in the synthesis of sex steroid hormones in gonadal and extra-gonadal tissues. In teleost species, although Hsd17b1 is recognized as essential for E2 synthesis, other Hsd17b types have recently been shown to have the potential to produce E2; however, information is limited. In this study, we isolated cDNA encoding Hsd17b7 from Japanese eels. We then characterized both hsd17b7 and hsd17b12a and compared their properties with those of hsd17b1 to identify the enzymes involved in E2 synthesis during ovarian development. The isolated hsd17b7 cDNAs putatively encoded 345 amino acid residues with conserved signatures of the short-chain dehydrogenase family. Recombinant Hsd17b7 and Hsd17b12a expressed in Human kidney 293T cells transformed androstenedione (A4) into testosterone (T) and estrone (E1) into E2. Tissue distribution analysis using quantitative real-time PCR revealed that hsd17b1, hsd17b7, and hsd17b12a mRNA were present in the ovaries of immature female Japanese eels. Furthermore, among the three hsd17bs, only hsd17b1 expression was upregulated during ovarian development. These results suggest that Hsd17b1, Hsd17b7, and Hsd17b12a are involved in E2 synthesis in the ovaries of the Japanese eel, and that Hsd17b1 plays a particularly important role in E2 production during oogenesis.

Physiological roles of ghrelin in the regulation of gastrointestinal motility in vertebrates.

Zhang S, Kaiya H, Kitazawa T

Gen Comp Endocrinol · 2025 Apr · PMID 40024446 · Publisher ↗

Ghrelin is known to be a multifunctional peptide hormone that stimulates not only growth hormone secretion and feeding but also gastrointestinal (GI) functions, including motility, secretion and mucosa proliferation. The... Ghrelin is known to be a multifunctional peptide hormone that stimulates not only growth hormone secretion and feeding but also gastrointestinal (GI) functions, including motility, secretion and mucosa proliferation. The aim of this review is to provide a comprehensive overview on the physiological roles of ghrelin in the regulation of GI motility from a comparative perspective. The effects of ghrelin on GI motility differ depending on the species, and ghrelin is a possible regulator of gastric migrating motor complexes (MMCs) in rodents, dogs and house musk shrew (suncus). However, the role of ghrelin has not been clarified in detail in other mammals, including humans and rabbits. Ghrelin is also effective to cause contraction in the GI tract of some non-mammals, but its physiological role is also not clarified at present. Distribution of the growth hormone secretagogue receptor (GHSR, ghrelin receptor) in the GI tract might be connected with the regulatory role of ghrelin in vertebrates. Comparative studies of ghrelin among animals and identification of knowledge gaps must lead us to the functional transition and importance of ghrelin in the GI tract.

Cortisol production by interrenal cells in rainbow trout (Oncorhynchus mykiss) is stimulated by 5-HT receptor activation.

Tea M, Dionne-Wilson LE, Bélair-Bambrick MÈ … +1 more , Gilmour KM

Gen Comp Endocrinol · 2025 Mar · PMID 40010613 · Publisher ↗

Although serotonin (5-HT) can stimulate the hypothalamic-pituitary-interrenal (HPI) axis in fishes, the sites of 5-HT action and the receptor subtypes involved remain unclear. Therefore, the present study identified pote... Although serotonin (5-HT) can stimulate the hypothalamic-pituitary-interrenal (HPI) axis in fishes, the sites of 5-HT action and the receptor subtypes involved remain unclear. Therefore, the present study identified potential sites of 5-HT action within the HPI axis of rainbow trout, Oncorhynchus mykiss, and examined which of three 5-HT receptor subtypes mediated effects of 5-HT on cortisol production. Expression of the receptors 5htr1a, 5htr2 and 5htr4 was detected at all three levels of the HPI axis, with significantly higher transcript abundance in the preoptic area (POA) of the brain than in the pituitary or head kidney. Administration of 300nmol kg 5-HT, but not 30nmol kg, to cannulated rainbow trout significantly increased circulating cortisol. Despite this cortisol response, no specific effects of 5-HT administration on POA transcript abundance of corticotropin-releasing factor (crf) or circulating adrenocorticotropic hormone (ACTH) concentrations were detected. To assess the direct actions of 5-HT on cortisol production, head kidney tissue was incubated in vitro with 5-HT or selective 5-HT receptor agonists. Neither the 5-HT receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) nor the 5-HT receptor agonist α-methyl-5-hydroxytryptamine maleate (α -methyl 5-HT) stimulated cortisol production. However, head kidney cortisol production was significantly increased by the 5-HT receptor agonist cisapride, an effect that was eliminated when tissue was incubated with a combination of cisapride and the 5-HT receptor antagonist GR125487. Collectively, these data support a role for 5-HT in HPI axis activation in rainbow trout, and suggest that effects of 5-HT in the head kidney are mediated by the 5-HT receptor.

Evaluating variation in acute stress response in captive Wood Ducks (Aix sponsa).

Broadus LJ, Hinton MG, Hahn TP … +3 more , Wingfield JC, Eadie JM, Makagon MM

Gen Comp Endocrinol · 2025 Mar · PMID 39984134 · Publisher ↗

Acute stress response has been linked to body condition and associated with the allocation of finite energy resources in wild, free-living birds. However, the relationship between the body condition of individuals and th... Acute stress response has been linked to body condition and associated with the allocation of finite energy resources in wild, free-living birds. However, the relationship between the body condition of individuals and the acute stress response is less clear for birds kept in captive settings, where energy resources are abundant and readily available. We evaluated how individual variation in body condition, reflected as body mass, relates to the acute stress response in adult captive Wood Ducks (Aix sponsa) hatched from eggs collected in the wild and reared in captivity while birds were fed ad libitum, in and out of the breeding season. We determined plasma corticosterone (CORT) levels from blood collected within 3 min of capture and at 10, 30, and 60 min post-capture from 28 ducks during spring and fall, in and out of breeding season. Body condition measurements were recorded once for each bird in early spring. The effects of body mass, age, and time of year (in vs. out of breeding season) on total and maximum CORT secreted were analyzed in Generalized Linear Mixed Models (GLMM). No relationships between age, body mass, and total or maximum CORT were found. There was a significant difference in response in and out of the breeding season for total CORT (p < 0.01) and maximum CORT (p < 0.001), with a higher response during the breeding season. Measures of individual responses for total (p = 0.001) and maximum CORT (p < 0.01) were consistent across seasons. Baseline CORT levels were consistently low, with 53.6 % and 78.6 % of the samples below the detection limit during and outside of breeding season, respectively. These results highlight differences in baseline CORT maintenance compared to studies on wild Wood Ducks, potentially relating to environmental differences such as unlimited food supply and protection from predators in captivity. Additionally, we found that captive birds maintain seasonal variation in acute stress response, which reflects some trends found in wild birds, although more research across multiple seasons is warranted. We also found that some captive Wood Ducks continue to increase CORT secretion at the end of the 60 min handling period, indicating that longer handling times may reveal differences in total CORT secreted. Further investigation should be done to assess the costs and benefits of variation in body condition in terms of coping ability across life stages.

The role of the opioid peptide dynorphin during the seasonal and gonadotropin-induced ovarian recrudescence in the gecko.

Ganeyan A, Ganesh CB

Gen Comp Endocrinol · 2025 Feb · PMID 39961516 · Publisher ↗

The aim of the current investigation was to elucidate the influence of the opioid peptide dynorphin-A (DYN) on the reproductive axis during breeding and non-breeding phases of the ovarian cycle in the gecko Hemidactylus... The aim of the current investigation was to elucidate the influence of the opioid peptide dynorphin-A (DYN) on the reproductive axis during breeding and non-breeding phases of the ovarian cycle in the gecko Hemidactylus frenatus. During the recrudescence phase, administration of a high dose of DYN (10 µg/0.1 ml saline) caused a significant reduction in the numbers of oogonia and primary oocytes in the germinal bed, compared to those of the initial controls or experimental controls. Administration of a low (2 µg DYN/0.1 ml saline) or high dose of DYN did not affect the follicular development up to stage IV, but there were no stage V (vitellogenic) follicles in the ovary in contrast to their presence in the experimental controls. Furthermore, there was a significant reduction in gonadotropin-releasing hormone-immunoreactive (GnRH-ir) content in the median eminence (ME) and pars distalis of the pituitary gland (PD) in low or high doses of DYN-treated lizards. During the regression phase, treatment with follicle-stimulating hormone (FSH) resulted in the appearance of stage IV and V follicles, in contrast to their absence in initial controls and treatment controls. However, treatment with 10 µg DYN + FSH did not promote the development of these follicles. In addition, in vitro treatment of DYN significantly inhibited ovarian levels of estradiol. Collectively, these findings reveal an inhibitory influence of DYN on the seasonal ovarian recrudescence, possibly mediated through the suppression of GnRH release into the ME and PD and directly at the level of the ovary by impairment in steroidogenesis and vitellogenic follicular growth in the gecko.

Hormonology: A kaleidoscopic tale of dedication, serendipity, and ingenuity.

Hsueh AJW, Li J

Gen Comp Endocrinol · 2025 Feb · PMID 39938725 · Publisher ↗

This article delves into stories of hormone discovery, characterization, clinical application, and the scientists themselves. Our journey begins with Arnold Berthod's rooster castration experiments, laying the groundwork... This article delves into stories of hormone discovery, characterization, clinical application, and the scientists themselves. Our journey begins with Arnold Berthod's rooster castration experiments, laying the groundwork for understanding testosterone, and Ernest Starling's 1902 revelation that secretin wasn't neuron-released. We'll explore the origins of kisspeptin and its role in Gonadotropin-releasing hormone pulsatile secretion by KNDY neurons. Discussions will then include the isolation of Growth hormone-releasing hormone from pancreatic tumors and growth hormone therapy's surprising link to Creutzfeldt-Jakob disease. We'll also delve into the design of long-acting follicle stimulating hormone for infertility treatment, alongside discoveries of five inhibin and activin hormones. Further, we'll uncover the discovery of receptors for relaxin family ligands and diverse chemokines, highlighting scientists' use of evolutionary genomics. We'll touch on parabiotic animal experiments leading to leptin's discovery and polarized ligand-receptor expression for receptor activation. The narrative will include instances such as a Nobel laureate who presented a rejection letter received prior to their award ceremony and a researcher pursuing receptor structure despite funding setbacks, both eventually rewarded. Through the diligent efforts of researchers and unexpected discoveries, the mechanisms of more than a hundred hormones have been elucidated. The endocrinological research domain is currently embracing the application of artificial intelligence to analyze extensive genomic and protein structure databases.

Effect of blocking transforming growth factor-β/Activin-Myostatin signaling on the expression of ecdysteroid metabolism and responsive genes in the crustacean molting gland (Y-organ).

Benrabaa SAM, Mykles DL

Gen Comp Endocrinol · 2025 Feb · PMID 39922321 · Publisher ↗

Molting in decapod crustaceans is controlled by ecdysteroids synthesized and secreted by the molting gland, or Y-organ (YO). The YO undergoes phenotypic changes in ecdysteroid production that drive molt cycle stage trans... Molting in decapod crustaceans is controlled by ecdysteroids synthesized and secreted by the molting gland, or Y-organ (YO). The YO undergoes phenotypic changes in ecdysteroid production that drive molt cycle stage transitions; these are the basal, activated, committed, and repressed states in the intermolt, early premolt, mid- and late premolt, and postmolt stages, respectively. Reduced secretion of molt-inhibiting hormone (MIH) by a neurosecretory center in the eyestalk ganglia activates the YO and the animal transitions to early premolt. During premolt, transforming growth factor-beta (TGFβ)/Activin-Myostatin (Mstn) signaling mediates the transition of the YO from the activated to the committed state, as SB431542 blocks this transition. In the blackback land crab, Gecarcinus lateralis, the YO expresses genes involved in ecdysteroid synthesis (Gl-NADK, Gl-ALAS and Halloween genes Gl-Nvd, Gl-Spo, Gl-Phm, Gl-Dib, and Gl-Sad) and catabolism (Gl-CYP18a1); ecdysteroid signaling (ecdysteroid responsive genes Gl-EcR, Gl-RXR, Gl-Br-C, Gl-HR3, Gl-HR4, Gl-E74, Gl-E75, and Gl-Ftz-f1); and Gl-FOXO. Intermolt adult G. lateralis were induced to molt by eyestalk ablation (ESA) and injected with either dimethyl sulfoxide (DMSO) vehicle (control) or SB431542 in DMSO (experimental) at Day 0. ESA increased hemolymph ecdysteroid titer at 1, 3, and 5 days post-ESA in both control and experimental groups, indicating that SB431542 had no effect on YO activation. Ecdysteroid titer did not increase further in the experimental group at 7 and 14 days post-ESA, indicating that SB431542 prevented transition of the YO to the committed state. ESA with or without SB431542 had no effect on the mRNA levels of the eight ecdysteroid metabolism genes, seven of the eight ecdysteroid responsive genes (the only exception was Gl-E74 at 1 day post-ESA), and Gl-FOXO at 1, 3, and 5 days post-ESA. Compared to the control group, SB431542 lowered the mRNA level of Gl-Nvd at 7 and 14 days post-ESA and mRNA levels of Gl-Spo, Gl-Phm, Gl-Dib, Gl-Sad, Gl-CYP18a1, Gl-ALAS, Gl-NADK, Gl-EcR, Gl-RXR, Gl-Br-C, and Gl-FOXO at 14 days post-ESA. SB431542 had no effect on the mRNA levels of Gl-HR3 Gl-HR4, Gl-E74, Gl-E75 and Gl-Ftz-f1. These results suggest that TGFβ/Activin-Mstn signaling maintains the mRNA levels of genes needed for increased ecdysteroid synthesis and signaling in the committed YO during mid- and late premolt.
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