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Gen. Comp. Endocrinol. [JOURNAL]

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Brain POMC Neurons: Comparative Aspects of Anatomy, Peptide Processing and Function.

Carr JA

Gen Comp Endocrinol · 2026 Jan · PMID 41213365 · Publisher ↗

Neurons that produce proopiomelanocortin (POMC), and the biologically active peptides derived from POMC, play essential roles in feeding, body mass regulation and analgesia. Despite the documented importance of POMC pept... Neurons that produce proopiomelanocortin (POMC), and the biologically active peptides derived from POMC, play essential roles in feeding, body mass regulation and analgesia. Despite the documented importance of POMC peptides as neuromodulators there are only two populations of cells in the mammalian brain that synthesize this prohormone. POMC neurons in the arcuate nucleus of the hypothalamus have a well-documented role in the long-term control of food intake and body mass. Emerging work suggests an important role for the brainstem population of POMC neurons in the rapid control of food intake. There remain, however, many questions about the roles played by differentially processed forms of melanocortin and endorphin peptides. While we know with certainty that all gnathostomes have an infundibular POMC neuronal group, there are many unanswered questions about the evolution of these neurons and their role in long term energy storage and nutrient signaling. Almost nothing is known about brainstem POMC neurons in non-mammalian vertebrates or the anatomy of POMC neurons systems in agnathans. In this review I will summarize what we know about the location, post-translational processing, and function of POMC peptides in the vertebrate brain.

Peptide and neuropeptide diversity and function in bivalves.

Li Z, Cardoso JCR, Power DM

Gen Comp Endocrinol · 2026 Jan · PMID 41213364 · Publisher ↗

The Mollusca are the second most specious animal phyla after arthropods. They are morphologically diverse and exhibit high variability of their nervous systems, which have evolved as they adapted to an extreme range of e... The Mollusca are the second most specious animal phyla after arthropods. They are morphologically diverse and exhibit high variability of their nervous systems, which have evolved as they adapted to an extreme range of ecological niches. Recent availability of genomes, transcriptomes and proteomes from diverse Mollusca representatives are uncovering the complexity of neuropeptides and their receptors. A diversity of neuropeptide precursors some of which encode multiple bioactive mature peptides and multiple orphan receptors have been described but their function is largely unexplored. This review will highlight the diversity of peptide/neuropeptide systems described in bivalves a member of the phylum Mollusca. The bivalves are of scientific and socioeconomic importance and in common with other calcifying marine organisms are susceptible to the effects of the rapidly changing global climate. Herein we briefly explore and compare mollusc nervous systems and highlight the complexity of bivalve peptide/neuropeptide genes, their putative receptor genes, and reports about their function in bivalve physiology. Characterization of the role of peptides/neuropeptides on bivalve physiology can give important insights into their evolutionary success but also feed models that can predict the likely impact of anthropogenic actions on their continuing success and biodiversity in a rapidly changing marine environment.

Seasonal vs opportunistic breeders, a seasonal morphological and endocrine comparative study of the gonadal cycle in birds.

Valdez DJ, López GC, Boaglio GI … +5 more , Uñates DR, López LM, Tempesti TC, Benitez-Vieyra SM, Somoza GM

Gen Comp Endocrinol · 2026 Jan · PMID 41207397 · Publisher ↗

Avian reproduction is usually seasonal and strongly influenced by environmental factors, primarily photoperiod, which is mainly perceived by deep brain photoreceptors in the hypothalamic region and regulates the activati... Avian reproduction is usually seasonal and strongly influenced by environmental factors, primarily photoperiod, which is mainly perceived by deep brain photoreceptors in the hypothalamic region and regulates the activation of the hypothalamic-pituitary-gonadal axis. However, certain species have developed adaptable reproductive strategies that differ from the classical seasonal model. In this study, we analyzed seasonal variations and gonadal asymmetry in three dove species with different reproductive strategies: The White-tipped Dove (Leptotila verreauxi) and the Eared Dove (Zenaida auriculata), both native to South America, and the Rock Dove (Columba livia), an introduced species from the Northern Hemisphere. Our results indicate that the White-tipped Dove, a seasonal breeder, follows a photoperiod-dependent reproductive pattern, showing seasonal variations in gonadal size and reproductive activity, as well as testosterone plasma levels, with no evidence of gonadal asymmetry. In the Eared Dove, an opportunistic breeder, the gonadal response is less pronounced, with testicular activity present even during months with short photoperiod, no association with testosterone plasma levels, and no gonadal asymmetry. Finally, the Rock Dove, another opportunistic breeder, exhibits the most variable gonadal response, with no association between photoperiod, gonadal morphology, and testosterone plasma levels. These findings suggest that the White-tipped Dove follows a classical photoperiod-regulated seasonal reproductive cycle, whereas the Eared Dove and the Rock Dove display greater reproductive plasticity, likely influenced by other factors, such as anthropogenic food availability, rather than photoperiod.

Relaxin receptor-like proteins in Scylla paramamosain: Two distinct types and their roles in ovarian development.

Du J, Huang Y, Liao J … +4 more , Zeng X, Zou P, Zhang Z, Wang Y

Gen Comp Endocrinol · 2026 Jan · PMID 41205658 · Publisher ↗

Scylla paramamosain, a vital marine economic crab species along the southeast coast of China, has been insufficiently studied regarding its reproductive regulation. Relaxin and its receptors play crucial roles in regulat... Scylla paramamosain, a vital marine economic crab species along the southeast coast of China, has been insufficiently studied regarding its reproductive regulation. Relaxin and its receptors play crucial roles in regulating animal reproductive processes. However, their functions and mechanisms of action in crustaceans remain unclear. In this study, two relaxin receptor-like proteins genes (SpRRLP) from S. paramamosain were cloned and designated as SpRRLP1 and SpRRLP2. Sequence analysis revealed that both belong to the C1 type of leucine-rich repeat type G-protein coupled receptors (LGR), with SpRRLP1 classified as an LGR4-type and SpRRLP2 as an RXFP/LGR3-type relaxin receptor. Temporal and spatial expression profiles demonstrated that both genes are most highly expressed in the ovary and eyestalk of mature crabs, with their expression levels significantly increasing during the middle and late stages of ovarian development. RNAi experiment combined with transcriptome analysis indicated that SpRRLP1 may be involved in ovarian development through pathways such as immunity, autophagy, and estrogen signaling, while SpRRLP2 primarily regulates ovarian development via pathways including the synthesis of sex steroid-like hormones and arachidonic acid metabolism. This study provides valuable insights into elucidating the mechanisms underlying gonadal development and reproductive regulation in crustaceans.

Melatonin modulates corticosterone-induced effects on steroidogenesis and reproductive-linked processes in male tree sparrow (passer montanus).

Yatung S, Ralte L, Trivedi AK

Gen Comp Endocrinol · 2026 Jan · PMID 41187878 · Publisher ↗

In birds, stressors increase corticosterone, a glucocorticoid, causing physiological, reproductive, and behavioural changes. Besides, melatonin, a neurohormone produced by the pineal gland, regulates circadian rhythms an... In birds, stressors increase corticosterone, a glucocorticoid, causing physiological, reproductive, and behavioural changes. Besides, melatonin, a neurohormone produced by the pineal gland, regulates circadian rhythms and seasonal reproduction and exhibits antioxidant properties. In the present study, photorefractory adult male tree sparrows were used. Body mass, bill colour, and testicular volume were recorded. Later, birds (n = 6/group) were divided into three groups and were treated for 4 weeks under 8L:16D light conditions: Group 1 received ethanolic saline (control), group 2 received corticosterone (2 µg/100 µl), and group 3 received corticosterone (2 µg/100 µl) plus melatonin (10 µg/100 µl), with melatonin administered 30 min before lights-off. After 4 weeks of treatment, the birds were subsequently shifted to 16L:8D for 30 days. At the experiment's end, samples were collected mid-light phase, and brain and testis tissues were stored at -80 °C for gene expression analysis. The study reveals no variation in the body mass and bill colour; however, testicular volume significantly increased across groups. Corticosterone treatment downregulated hypothalamic reproductive transcripts in tree sparrows, while the corticosterone plus melatonin and control groups showed upregulation of these genes. Furthermore, steroidogenic genes were downregulated in the testis of the corticosterone group compared with the other groups. Similarly, epigenetic genes (Hdac1, Hdac3, and Dnmt1) were upregulated in the hypothalamus in the corticosterone group; however, no changes were observed in the testis. These findings indicate corticosterone negatively impacts reproductive and steroidogenic activity in tree sparrows, but melatonin mitigates these effects, enhancing reproductive-linked steroidogenesis. This suggests a protective role of melatonin in counteracting corticosterone-induced reproductive suppression in this species.

Reproductive status affects stress-induced hormonal and immune changes in male and female Rhinella diptycha toads.

Titon SCM, Titon Junior B, Assis VR … +2 more , Lima AS, Gomes FR

Gen Comp Endocrinol · 2026 Jan · PMID 41177272 · Publisher ↗

Species with seasonal reproduction exhibit marked variations in physiological processes, including reproductive physiology and immune functions. In unpredictable situations, the emergency life-history stage is characteri... Species with seasonal reproduction exhibit marked variations in physiological processes, including reproductive physiology and immune functions. In unpredictable situations, the emergency life-history stage is characterized by a stress response, primarily mediated by glucocorticoids, which regulate the balance between survival and reproduction. To better understand the impact of stressful events on endocrine and immune physiology in amphibians, we subjected male (calling or foraging) and female (foraging) toads (Rhinella diptycha) captured in the field during a reproductive event to a restraint protocol (0 h, 1 h, and 24 h, repeated samples). Before the restraint, a blood sample was collected to obtain reference values for plasma hormone levels (corticosterone, the main glucocorticoid in amphibians; testosterone; and estradiol) and immune measures (plasma bacterial killing ability and the neutrophil-to-lymphocyte ratio). Plasma corticosterone levels increased 1 and 24 h post-restraint in females and males (regardless of activity). We found decreased estradiol and testosterone plasma levels 24 h post-restraint, regardless of sex or activity. The plasma bacterial killing ability increased 1 h post-restraint in calling males and decreased 24 h post-restraint irrespective of sex or activity. The neutrophil to lymphocyte ratio increased only in foraging males 24 h post-restraint compared with 1 h post-restraint. These findings indicate that while corticosterone responses to acute stress are rapid and persist over time, the suppression of sex steroids and certain immune functions becomes more evident under prolonged stress exposure. Moreover, the transient enhancement of bacterial killing ability in calling males and the delayed increase in neutrophil-to-lymphocyte ratio in foraging males suggest that stress-induced immunomodulation may be influenced by reproductive behavior in R. diptycha.

Comprehensive adrenal steroid profiling during frog metamorphosis.

Paul B, Patel S, Taylor AJ … +2 more , La Frano MR, Buchholz DR

Gen Comp Endocrinol · 2026 Jan · PMID 41161611 · Publisher ↗

Measurement of adrenal hormones in amphibians is important in studies on stress, development, osmoregulation, endocrine disruption, and conservation to help reveal mechanisms within amphibians and evolution among vertebr... Measurement of adrenal hormones in amphibians is important in studies on stress, development, osmoregulation, endocrine disruption, and conservation to help reveal mechanisms within amphibians and evolution among vertebrates. Corticosteroids measured in frogs are typically corticosterone and/or aldosterone, but steroid intermediates that may activate hormone receptors are thus far not quantified. Also, steroidogenesis in frogs has been examined in vitro but little work has been done using tadpoles with mutations affecting steroidogenesis. To advance such studies, we developed a comprehensive liquid chromatography - tandem mass spectrometry (LC-MS/MS) method to quantify 13 corticosteroid hormones and intermediates and 5 sex steroids in plasma and tail during natural metamorphosis and in pomc and cyp21a2 mutant tadpoles. Four of these steroids were consistently quantified in plasma and tail during development of wild-type tadpoles, namely 11-deoxycorticosterone (11-DOC), corticosterone (CORT), aldosterone (ALDO), and 11-dehydrocorticosterone (11-dehydroCORT). During metamorphosis, each of these steroids increased 4- to 5-fold in plasma, whereas in tail they were high during premetamorphosis and climax but lower in prometamorphosis. pomc mutant tails had only 2-fold less CORT, but cyp21a2 mutants also had an accumulation of progesterone and 11β-hydroxyprogesterone. This study revealed the in-vivo presence of 11-DOC, 11-dehydroCORT, and adrenal steroidogenic capacity in tadpoles and provided a comprehensive LC-MS/MS method for quantifying steroids relevant for a wide variety of studies.

Comparative corticosterone responses to capture stress in sympatric Antarctic penguins.

Machado Pinto JA, Souza-Kasprzyk J, Guilherme Padilha JA … +4 more , Viau P, Machado Torres JP, Alves MAS, Costa ES

Gen Comp Endocrinol · 2025 Nov · PMID 41115535 · Publisher ↗

Adverse environmental stimuli activate the hypothalamic-pituitary-adrenal axis, releasing corticosterone (CORT), the primary stress hormone in birds. This hormone facilitates adaptive responses to acute stressors, ensuri... Adverse environmental stimuli activate the hypothalamic-pituitary-adrenal axis, releasing corticosterone (CORT), the primary stress hormone in birds. This hormone facilitates adaptive responses to acute stressors, ensuring immediate survival but potentially compromising other vital functions when chronically elevated. In penguins, particularly those of the genusPygoscelis, there is a striking lack of comparative data on stress physiology, especially for chicks, despite their ecological importance as bioindicators of Antarctic ecosystem change. Understanding species and age-specific stress responses is essential given their shared habitat, contrasting behavioral traits, and increasing exposure to climate change-related stressors. This study investigated the effects of capture and restraint on CORT concentrations in three sympatric penguin species: P. adeliae(Adélie),P. papua(Gentoo), andP. antarcticus(Chinstrap) nesting on King George Island, Antarctica. Blood samples were collected from adults and chicks of P. adeliae (n = 25 and n = 8) and P. antarcticus (n = 18 and n = 10), and from adults of P. papua (n = 18) at baseline (within 5 min of capture, CORT) and after restraint for 30, 45, or 60 min (CORT, CORT, CORT). Opportunistic urofecal samples (n = 36) were also analyzed from adults of the three species to compare excreted hormone levels with circulating one. All species showed a significant and non-linear increase in blood CORT following capture. Concentrations peaked at 30 min post-capture in P. adeliaeand P. Papua which showed a pattern of initial increase followed by a temporary decline and secondary rise in corticosterone levels,whereas P. antarcticushad a more gradual and progressive increase over time peaking at 45 min. Interestingly,P. antarcticuschicks exhibited higher CORT concentrations than adults, potentially reflecting greater reactivity to stress, whereasP. adeliaechicks showed values similar to adults, consistent with a maturing stress response. Urofecal CORT concentrations did not significantly differ among species but were consistently higher than baseline blood levels, likely reflecting integrated stress over time. This is the first study to compare baseline and stress-induced CORT concentrations across all threePygoscelisspecies, to measure CORT in adults and chicks ofP. antarcticus, and to analyze Pygoscelis populations from King George Island. By filling critical gaps in penguin stress physiology, these findings contribute to understanding interspecific and developmental variation in endocrine responses, confirm that capture and restraint significantly alter corticosterone levels and highlight the need for careful consideration of capture and handling procedures in wildlife research and conservation practices.

Immunohistochemical detection of teleost- and mammalian-type melanin-concentrating hormone in goldfish brain with newly developed specific antibodies.

Yang T, Shinohara Y, Otake-Oda M … +6 more , Nakagawa Y, Kodera Y, Ikegami K, Amano M, Mizusawa K, Takahashi A

Gen Comp Endocrinol · 2025 Nov · PMID 41093068 · Publisher ↗

In teleosts, melanin-concentrating hormone (MCH) is involved in body color change, feeding, and sleep regulation. The distribution of MCH neurons in the brain and pituitary must be clarified to understand diverse functio... In teleosts, melanin-concentrating hormone (MCH) is involved in body color change, feeding, and sleep regulation. The distribution of MCH neurons in the brain and pituitary must be clarified to understand diverse functions of MCH in the brain. This study aimed to discriminate neurons producing teleost-type MCH (MCH-like, MCHL) and mammalian-type MCH (MCH) in the brain and pituitary of goldfish Carassius auratus by immunohistochemistry using specific antibodies. Since the mature MCH region is not available for specific peptide antigen, we selected peptides derived from non-MCH regions on proMCH (PMCH). Nano Liquid Chromatography with tandem mass spectrometry analysis showed that both PMCHL and PMCH are cleaved into smaller peptides at mono- and dibasic-amino acid as well as non-basic sites. Based on these findings, PMCHLa (72-90) and PMCHa (88-102) were synthesized and used for immunization. The results of immunohistochemistry using thus prepared antibodies showed that neurons containing PMCHLa and PMCHa are differentially distributed in the hypothalamus and pituitary of goldfish. PMCHLa-immunoreactive (ir) fibers were detected in several brain regions, while PMCHa-ir fibers were confined to the hypothalamic area. The antibodies developed in the present study would contribute to clarify the role of the teleost-type and mammalian-type MCH.

Stress signaling via glucocorticoid receptor disrupts ovarian development in Japanese eel (Anguilla japonica) through HPI-HPG axis crosstalk.

Zhang X, Zuo C, Liu J … +5 more , Jing X, Zhao Z, Yang J, Wang Z, Qi X

Gen Comp Endocrinol · 2025 Nov · PMID 41077224 · Publisher ↗

Gonadal development is closely linked to cortisol levels, a major stress response indicator, which is mediated by the glucocorticoid receptor (GR) in teleost fish. Stress activates the HPI axis (hypothalamic-pituitary-ad... Gonadal development is closely linked to cortisol levels, a major stress response indicator, which is mediated by the glucocorticoid receptor (GR) in teleost fish. Stress activates the HPI axis (hypothalamic-pituitary-adrenocortical axis), triggering cortisol release, which subsequently affects the reproductive system. Therefore, GR is considered a mediator in elucidating the relationship between stress and gonadal development. In this study, we cloned and analyzed the gr1 and gr2 genes of the Japanese eel (Anguilla japonica). The phylogenetic tree of GR revealed that gr1 and gr2 exhibit a unique evolutionary distribution in teleost fish. Quantitative real-time PCR results indicated that gr1 and gr2 were primarily expressed in the ovary and brain. To investigate whether glucocorticoids mediate their inhibitory effects through GR, we performed in vivo DXMS injection experiments. The results indicated that DXMS stimulation significantly altered the expression of key genes in the HPG axis (hypothalamic-pituitary-gonadal axis) of the Japanese eel, particularly those related to ovarian development. Additionally, in vitro experiments with isolated brain, pituitary, and gonadal cells revealed that DXMS treatment significantly suppressed the expression of several reproduction-related genes, and the GR antagonist RU486 partially reversed this suppression. This study reveals the mechanisms through which glucocorticoids regulate ovarian development in the Japanese eel via GR and HPI-HPG axis interactions. These findings offer new insights into the role of stress in fish reproduction and provide a theoretical basis for optimizing artificial reproduction techniques in the Japanese eel.

Melatonin suppresses the seasonal estrus in female giant pandas.

Huang H, Hou R, Kersey DC … +7 more , Lan J, Ye Z, Li Y, Yao Y, Cai K, Hu X, Liu Y

Gen Comp Endocrinol · 2025 Oct · PMID 41047045 · Publisher ↗

In mammals, the pineal gland secretes melatonin, which serves as a crucial signal for interpreting photoperiod cues. As a seasonal breeder, the giant panda typically mates during the spring. To fully elucidate melatonin'... In mammals, the pineal gland secretes melatonin, which serves as a crucial signal for interpreting photoperiod cues. As a seasonal breeder, the giant panda typically mates during the spring. To fully elucidate melatonin's influence on the seasonal estrus of female giant pandas, we conducted an in-depth analysis of urinary hormones. First, we found that urinary melatonin and gonadotropin-releasing hormone (GnRH) levels exhibit distinct seasonal variations over the annual cycle. From January to April, melatonin levels decline sharply from their annual peak, while GnRH levels rise rapidly and remain elevated throughout February, March, and April, precisely corresponding to the giant panda breeding season. Second, during female estrus, the estrogen metabolites peak occurs near the time when melatonin levels drop to their lowest values, and an inverse correlation between melatonin and estrogen metabolites persists both before and after the estrogen metabolites peak. Our analysis of urinary hormones revealed that melatonin exerts a significant suppressive effect on urinary GnRH and estrogen metabolites production prior to the onset of the seasonal estrus in giant pandas. Given the multipotent differentiation capacity of mesenchymal stem cells, we selected cultured giant panda umbilical cord mesenchymal stem cells (UC-MSCs) as an in vitro model for further study. Initially, we characterized the expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in UC-MSCs following GnRH stimulation. Notably, these cells exhibited pituitary-like functional properties, including responsiveness to GnRH and expression of FSH and LH genes, making them suitable for modeling melatonin's effects. Subsequent experiments demonstrated that melatonin suppresses GnRH-induced LH and FSH mRNA expression in UC-MSCs in a dose-dependent manner and higher concentrations of melatonin were particularly effective. Collectively, our study not only elucidates the regulatory effects of melatonin on the seasonal estrous cycle of female giant pandas but also offers valuable new perspectives. These insights can potentially guide the development of conservation strategies for this endangered species, facilitating more targeted and effective efforts to safeguard its population.

Synthesis of sex steroids and expression of sex steroid receptors during gonadal development of the snail-eating turtle Malayemys macrocephala (Gray, 1859).

Pewphong R, Watanabe G, Nagaoka K … +3 more , Kitana J, Thitiphuree T, Kitana N

Gen Comp Endocrinol · 2025 Nov · PMID 41047044 · Publisher ↗

Prior studies on the freshwater turtle Malayemys macrocephala showed that the incubation temperature influenced somatic and gonadal development, supporting temperature-dependent sex determination. This study aimed to exa... Prior studies on the freshwater turtle Malayemys macrocephala showed that the incubation temperature influenced somatic and gonadal development, supporting temperature-dependent sex determination. This study aimed to examine the onset of steroidogenesis and expression of steroid receptors during gonadal development of M. macrocephala. Embryos at the sexually undifferentiated gonad (stages 14-16), differentiating gonad (stages 17-22), and differentiated gonad (stages 23-25) stages reared at the male- and female-producing temperatures (26 °C and 32 °C, respectively) were examined. Gonads were assessed for steroidogenic potential by immunofluorescence staining using antibodies against 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD), and P450 aromatase (P450arom), as well as the androgen receptor (AR) and estrogen receptor α (ERα). In males, expression of these steroidogenic enzymes and steroid receptors were found as follows: 3β-HSD at stages 14-22, 17β-HSD at stages 14-25, and AR at stages 17-25. In females, the expression was as follows: 3β-HSD and 17β-HSD at stages 14-22, P450arom at stages 19-25, and ERα at stages 19-25. Overall, the results suggest that in gonadal development of M. macrocephala: 3β-HSD plays a role as a key enzyme in the biosynthesis of sex steroids, 17β-HSD and the AR play roles in testis development, and P450arom and the ERα are involved in ovary development.

Does motilin primarily regulate gastrointestinal motility in fish?

Kitazawa T, Kaiya H, Zhang S

Gen Comp Endocrinol · 2025 Oct · PMID 41015347 · Publisher ↗

Motilin (MLN) is a gut motility-stimulating peptide hormone that regulates the gastric migrating motor complex in humans, dogs, monkeys, and house musk shrews (Suncus). MLN and its receptors are found not only in mammals... Motilin (MLN) is a gut motility-stimulating peptide hormone that regulates the gastric migrating motor complex in humans, dogs, monkeys, and house musk shrews (Suncus). MLN and its receptors are found not only in mammals but also in other vertebrates (birds, reptiles, amphibians, and fish). This review focuses on the physiological roles of MLN in fish. Fish MLNs are produced in the mucosa of the upper small intestine. MLNs in amphibians, reptiles, birds, and mammals are 22-amino-acid peptides with phenylalanine at the first position of the N-terminus, except for reptile MLNs. In contrast, fish MLNs are shorter, and the N-terminal starts with histidine instead of phenylalanine. The function of MLN can be inferred from the distribution of MLN receptors. MLN receptors are commonly expressed in the central nervous system and gastrointestinal (GI) tract of fish, as in mammals. In the central nervous system, MLN is thought to be involved in the regulation of feeding and drinking. However, MLN receptors in the fish GI tract are limited to the intestinal mucosa, and MLN fails to induce contraction in the fish GI tract. In amphibians, birds, and mammals, the expression of MLN receptors extends to GI smooth muscles and enteric neurons and is involved in the regulation of GI motility. These findings suggest that MLN is not a regulator of GI motility in fish, but instead regulates the functions of intestinal mucosal cells and central neurons.

Aldosterone increased by chronic unpredictable mild stress damages epididymal sperm quality in young rats.

Osorio Pérez TG, Pérez-Sánchez E, Nolasco Garduño VG … +5 more , Corona-Pérez A, de Lourdes Arteaga Castañeda M, Lucio RA, Rodríguez-Antolín J, Nicolás-Toledo L

Gen Comp Endocrinol · 2025 Oct · PMID 40998182 · Publisher ↗

In young rats, aldosterone concentration increases in response to stress. Aldosterone can decrease testosterone production. We hypothesized that aldosterone impairs sperm quality, and that this impairment is reversible w... In young rats, aldosterone concentration increases in response to stress. Aldosterone can decrease testosterone production. We hypothesized that aldosterone impairs sperm quality, and that this impairment is reversible with 50 mg/kg of eplerenone in young rats. Forty-two young male Wistar rats (51 days old) were divided into six groups: Control, Control + vehicle (C + Veh), chronic unpredictable mild stress (CUMS), and CUMS + eplerenone at three concentrations: 25, 50, and 100 mg/kg bw, a selective aldosterone blocker (CUMS + EP) (n = 7 per each). On postnatal day 51, eplerenone was administered orally via gastric tube 2 h before the start of the stress test. The CUMS paradigm was administered once daily at various times, without repeating the stressor, over a four-week period. We evaluated the effects of chronic stress on serum testosterone concentrations, oxidative stress, apoptosis, and sperm quality. The CUMS group exhibited low testosterone levels and poor epididymal sperm quality. Compared to the CUMS group, the 50 mg/kg dose of eplerenone demonstrated significant improvements in sperm motility (28.8 %), sperm viability (36.9 %), and sperm concentration (58.9 %). In the CUMS context, the 100 mg/kg dose was toxic because it induced oxidative stress and apoptosis. Aldosterone negatively affects epididymal sperm quality by reducing testosterone-induced sperm motility, viability, and concentration. Aldosterone impairs sperm quality, which is reversible with 50 mg/kg of eplerenone. The prevention by eplerenone supports our hypothesis.

Expression of the estrogen receptor gene across the life cycle in the polychaete, Capitella teleta.

Murillo AM, Lanza AR, Hendershot M … +3 more , Setton EVW, Seaver EC, Wilson JY

Gen Comp Endocrinol · 2025 Oct · PMID 40983133 · Publisher ↗

Vertebrate estrogen receptors (ERs; NR3A subfamily genes) are essential for regulating multiple biological processes in vertebrates. However, little is known about ERs (NR3D subfamily genes) in invertebrates. Capitella t... Vertebrate estrogen receptors (ERs; NR3A subfamily genes) are essential for regulating multiple biological processes in vertebrates. However, little is known about ERs (NR3D subfamily genes) in invertebrates. Capitella teleta is a marine polychaete with a single ER gene that is ligand-activated with low concentrations of estradiol in vitro; yet the physiological role of this receptor is unclear. We used whole-mount in situ hybridization to investigate spatial and temporal expression patterns of the ER in larval stages and RT-qPCR to detect temporal ER gene expression patterns across age and sex in juvenile and adults. The ER gene was expressed in the brain and foregut across multiple larval stages, suggesting a role in brain and gastrointestinal development. Whole-body juvenile ER gene expression was similar between two and six weeks of age. ER expression was similar across sex between head fragments, gastrointestinal systems, or whole bodies of sexually mature worms. These data show that the ER does not exhibit a sexually dimorphic expression as is stereotypical in vertebrates, and suggests that the ER may may not play a big role in sexual maturation in C. teleta. Collectively, ER is expressed across multiple life stages and suggests a role in brain and foregut development, and possibly a gastrointestinal function in adults. This study aids in uncovering the physiological functions of ER in lophotrochozoans.

Impact of artificial light at night and night shift work on brain functions and metabolism.

Korf HW, Bittner N, Caspers S … +1 more , von Gall C

Gen Comp Endocrinol · 2025 Oct · PMID 40976568 · Publisher ↗

The present review focusses on artificial light at night (ALAN) and night shift work (NSW) as examples for chronodisruption occurring in modern societies. Chronodisruption can lead to significant sleep and health problem... The present review focusses on artificial light at night (ALAN) and night shift work (NSW) as examples for chronodisruption occurring in modern societies. Chronodisruption can lead to significant sleep and health problems and increase the risk of chronic diseases. This pathomechanism involves endocrine systems (glucocorticoids, melatonin). ALAN affects at least 80% of mankind and disturbs physiological, biological and behavioral processes in wildlife. In humans, the nighttime use of illuminated screens contributes to ALAN, with as yet unforeseeable consequences for body and brain. Acute continuous light exposure triggers pro-inflammatory responses in the brain which may make it more vulnerable to additional aversive stimuli. Moreover, acute continuous light impairs cognitive function and synaptic plasticity and leads to an increase in corticosterone, a stress hormone and an important mediator in the circadian system. Several studies on NSW reported increased risk for sleep disorders, cancer, cardiovascular disease, type 2 diabetes, obesity, and depression. However, objective imaging analyses supplemented by neuropsychological examinations revealed that NSW has only minor effects on brain functions. Moreover, a recent study showed that NSW was not accompanied by metabolic, cardiovascular or immunological problems. In conclusion, ALAN may be considered a relevant factor influencing human health and biodiversity and should be avoided whenever possible. Studies on the effects of NSW report varying results. This may be due to differences in light intensity during shift, the quality of the occupational health service and the shift work schedule. All these aspects need further investigations to prevent or mitigate the health risk of NSW.

Identification and functional characterization of relaxin-like gonad stimulating peptide in the sea cucumber, Stichopus horrens.

Goodearly TR, Wirth-Yap A, Fox BK … +2 more , Katayama H, Seale AP

Gen Comp Endocrinol · 2025 Oct · PMID 40975135 · Publisher ↗

In the state of Hawai'i, there is rising interest in the culture of native sea cucumbers, such as Stichopus horrens; however, current production is hindered by a limited understanding of their reproductive biology. Origi... In the state of Hawai'i, there is rising interest in the culture of native sea cucumbers, such as Stichopus horrens; however, current production is hindered by a limited understanding of their reproductive biology. Originally described in starfish, relaxin-like gonad stimulating peptide (RGP) has been characterized and used to induce oocyte maturation and spawning in sea cucumbers. For the first time using S. horrens specifically, we identified the RGP (Sh-RGP) coding sequence through de novo transcriptomics, synthesized the mature peptide, and investigated its role in inducing oocyte maturation in vitro, and spawning in vivo. The Sh-RGP precursor gene encodes a single mature peptide composed of two amino acid chains. The B- and A-chains contain two and four cysteine residues, respectively, resulting in an intra-chain linkage on the A-chain and two disulfide connections between the two chains. A synthetic Sh-RGP was produced from solid-phase peptide synthesis, bonded, and isolated by reverse-phase HPLC. A tissue distribution analysis revealed that shrgp mRNA expression is highest (P<0.001) in the neural ring. In vitro, Sh-RGP (0.1-10 μM) induced germinal vesicle breakdown in oocytes incubated with gonadal tissue in time and concentration-dependent fashions. When injected with Sh-RGP (∼4.5 μg/kg body weight), all mature male and female sea cucumbers spawned within 39 min of treatment. Overall, these results indicate that Sh-RGP induces oocyte maturation and spawning and provide a framework for integrating transcriptomics and functional assays to elucidate and validate endogenous species-specific reproductive hormones that can be used to address barriers in sea cucumber aquaculture.

Photoperiod-dependent expression of 'Cocaine- and amphetamine-regulated transcript peptide' and 'Neuropeptide Y' in the brain of anuran Minervarya syhadrensis.

Shetye K, Sagarkar S, Shewale S … +3 more , Sakharkar A, Bhargava S, Ashma R

Gen Comp Endocrinol · 2025 Oct · PMID 40972741 · Publisher ↗

Anurans exhibit diurnal behavioral patterns; however, the expression of neuropeptides that modulate these activities remains unexplored. This study investigates day-night expression patterns of Cocaine- and Amphetamine-R... Anurans exhibit diurnal behavioral patterns; however, the expression of neuropeptides that modulate these activities remains unexplored. This study investigates day-night expression patterns of Cocaine- and Amphetamine-Regulated Transcript Peptide (CARTp) and Neuropeptide Y (NPY) in the brain of nocturnal frog, Minervarya syhadrensis. Frogs were sacrificed at different timepoints (1) under normal day-night conditions (2) after exposure to 24 h darkness and (3) 24 h light. Brain tissues, including the olfactory system, were collected for immunohistochemical analysis. Photoperiod-dependent alterations in expression of CART and NPY were observed in various brain regions. According to cosine analysis, the oscillation was seen only in the olfactory epithelium (OE) with maxima at 11:00. In anteroventral tegmentum (AV), CARTp and NPY expression were highest at midnight. In few brain regions, NPY or CARTp oscillations were observed. NPY oscillations were seen in preoptic area (POA), with a peak at noon, and in suprachiasmatic nucleus (SCN), anterior ventral hypothalamus (AvHy), and nucleus isthmus (NI) highest expression was at midnight. In Edinger-Westphal nucleus (EW) and posterior ventral hypothalamus (PvHy) CARTp upregulation was observed at midnight. CARTp fluctuated in OE, PvHy, and EW on light exposure, while changes in NPY expression were seen in OE, POA and SCN. Photoperiod-dependent fluctuations in both peptides were noted in OE and AV. While on exposure to darkness, CARTp expression decreased in AV, PvHy, and EW, and NPY expression was affected in AV, POA, SCN, AvHy, and NI. These results suggest neuropeptides in anurans exhibit photoperiod-dependent differential expression, potentially regulating physiological functions and behavioral patterns.

Corticotropin-releasing hormone enhances the responsivity of macrophages to inflammation in zebrafish.

van Heijningen J, van der Pluijm LHM, Schaaf MJM … +1 more , Faught E

Gen Comp Endocrinol · 2025 Oct · PMID 40957546 · Publisher ↗

The immunomodulatory role of steroid stress hormones, such as cortisol, are well characterized; however, less is known about how other stress hormones affect the immune system. Release of central corticotropin-releasing... The immunomodulatory role of steroid stress hormones, such as cortisol, are well characterized; however, less is known about how other stress hormones affect the immune system. Release of central corticotropin-releasing hormone (Crh) will result in an indirect anti-inflammatory effect due to the stimulation of cortisol production. Conversely, peripheral release of Crh is thought to directly exhibit proinflammatory effects on leukocytes. This suggests that the peripheral Crh system promotes inflammation, rather than suppresses it, but the molecular mechanisms are not well defined. To test the hypothesis that Crh will stimulate immune function, we used the zebrafish animal model and assessed leukocyte migration towards a wound as a readout of inflammatory capacity. We show that not only is crhr1 regulated during inflammation, but that it directly modulates the leukocyte population localized to a wound site. In particular, it enhances pro-inflammatory macrophage recruitment through the Cxcr3.2/Cxcr11aa signalling axis. Taken together, this work further contributes to our understanding of how Crh, and stress as a whole, can impact immune system function.

Putative genes coding for pituitary adenylate cyclase-activating polypeptide and immunohistochemical localization of their mature peptides in the brain-pituitary axis of the inshore hagfish Eptatretus burgeri.

Amano M, Furuya S, Yamamoto N … +3 more , Yamaguchi Y, Sekiguchi T, Osugi T

Gen Comp Endocrinol · 2025 Nov · PMID 40953711 · Publisher ↗

Hagfish and lampreys, which are both members of the class Agnatha, are widely considered to represent one of the most basal evolutionary lineages of vertebrates. Pituitary adenylate cyclase-activating polypeptide (PACAP)... Hagfish and lampreys, which are both members of the class Agnatha, are widely considered to represent one of the most basal evolutionary lineages of vertebrates. Pituitary adenylate cyclase-activating polypeptide (PACAP) and growth hormone-releasing hormone (GHRH) are both members of the secretin/PACAP family. We searched the Ensembl database for putative PACAP and GHRH sequences in the inshore hagfish, Eptatretus burgeri. We identified three putative GHRH/PACAP precursors (hagfish-1/2/3) whose expression in various tissues, including the brain, was confirmed using RNA sequencing. The hagfish-1 precursor encodes both GHRH/PRP (PACAP-related peptide) and PACAP, whereas the hagfish-2 and -3 precursors encod only PACAP. Of the three putative hagfish PACAPs, PACAP-2, encoded by hagfish-2, showed relatively high identity (77.8%) and similarity (85.2%) with PACAP from other species. In contrast, hagfish GHRH/PRP encoded by hagfish-1 showed low identity (27.3%) and similarity (50.3%) with other GHRHs, and low identity (26.7%) and similarity (46.7%) with other PRPs. Phylogenetic analysis confirmed that the hagfish-2 sequence clustered within the same clade as lamprey PACAP. PACAP-like-immunoreactive (ir) cell bodies and dense punctate fibers have been detected in several brain regions, including the preoptic area, infundibular nucleus of the hypothalamus, midbrain tegmentum, and medulla oblongata. In the pituitary gland, PACAP-like-ir fibers were observed in the dorsal wall of the neurohypophysis. GHRH/PRP immunoreactivity was also observed in the medulla oblongata. The present study demonstrated that PACAP-like- and GHRH/PRP-like peptides are expressed in the brain of the inshore hagfish E. burgeri.
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