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• Maternal stress is linked to PTSD-like symptoms in offspring and HPA axis dysregulation. • Paternal stress is associated with physiological disturbances in offspring, but neuroendocrine features are ill-defined. • Rodent models of paternal stress indicate an intergenerational shift in anxiety-related behaviours. • HPA axis regulation and physiological stress response is currently under-studied in rodent models. There is increasing evidence that one's risk for psychiatric disturbances and metabolic syndromes is influenced by their parents' own health history, lifestyle and living environment. For example, paternal high fat diet is strongly linked to neuroendocrine dysregulation in offspring and increased risk for diabetes. The potential intergenerational impact of paternal stress has only just begun to emerge, with the initial evidence suggestive of greater risk for anxiety-related disorders. The hypothalamic–pituitary–adrenal (HPA)-axis is a key neuroendocrine signalling system involved in physiological homeostasis and stress response. In individuals, dysregulation of this system is closely associated with behavioral deficits and mood disorders. Various preclinical models of paternal stress have demonstrated robust behavioral shifts but little is known about the intergenerational modification of HPA axis function. This review will present evidence drawn from a range of laboratory mouse and rat models that the intergenerational influence of paternal stress on offspring behavioral phenotypes involve some level of HPA axis dysregulation. It makes the case that further investigations to comprehensively profile HPA axis function in offspring generations is warranted. [ABSTRACT FROM AUTHOR]

• The HPI-axis of tilapia facing salinity challenges was characterized. • Circulating cortisol was generally unaffected by salinity challenges. • Pituitary pomc expression was higher in fish in SW compared with those in FW. • Branchial corticosteroid receptor expression decreased in FW in both transfer and tidal paradigms. In estuarine environments, euryhaline fish maintain a narrow range of internal osmolality despite daily changes in environmental salinity that can range from fresh water (FW) to seawater (SW). The capacity of euryhaline fish to maintain homeostasis in a range of environmental salinities is primarily facilitated by the neuroendocrine system. One such system, the hypothalamic-pituitary-interrenal (HPI) axis, culminates in the release of corticosteroids such as cortisol into circulation. Cortisol functions as both a mineralocorticoid and glucocorticoid in fish because of its roles in osmoregulation and metabolism, respectively. The gill, a key site for osmoregulation, and the liver, the primary storage site for glucose, are known targets of cortisol's actions during salinity stress. While cortisol facilitates acclimation to SW environments, less is known on its role during FW adaptation. In this study, we characterized the responses of plasma cortisol, mRNA expression of pituitary pro-opiomelanocortin (pomc), and mRNA expression of liver and gill corticosteroid receptors (gr1, gr2, and mr) in the euryhaline Mozambique tilapia (Oreochromis mossambicus) under salinity challenges. Specifically, tilapia were subjected to salinity transfer regimes from steady-state FW to SW, SW to FW (experiment 1) or steady state FW or SW to tidal regimen (TR, experiment 2). In experiment 1, fish were sampled at 0 h, 6 h, 1, 2, and 7 d post transfer; while in experiment 2, fish were sampled at day 0 and day 15. We found a rise in pituitary pomc expression and plasma cortisol following transfer to SW while branchial corticosteroid receptors were immediately downregulated after transfer to FW. Moreover, branchial expression of corticosteroid receptors changed with each salinity phase of the TR, suggesting rapid environmental modulation of corticosteorid action. Together, these results support the role of the HPI-axis in promoting salinity acclimation, including in dynamically-changing environments. [ABSTRACT FROM AUTHOR]

Highlights • Localization of PrRP2 in the brain of the inshore hagfish was examined. • PrRP2-ir cell bodies were detected in the infundibular nucleus of hypothalamus. • PrRP2-ir fibers were restricted around PrRP2-ir cell bodies. • PrRP2-ir fibers were not detected in the dorsal wall of the neurohypophysis. • Reciprocal connections are suggested between the PrRP2 and PQRFa neurons. Abstract Prolactin-releasing peptide2 (PrRP2) belongs to the RFamide peptide group and is a paralog of prolactin-releasing peptide (PrRP). Recent studies demonstrated that PrRP2, but not PrRP, regulates prolactin release in teleosts. The evolutionary origin of PrRP and PrRP2 dates back to at least early vertebrates because homologs of PrRP/PrRP2 were identified in lampreys, one of the earliest branch of vertebrates class Agnatha. However, PrRP/PrRP2 remains to be identified in hagfish, another representative species of class Agnatha. Here, we examined the distribution of PrRP2 in the brain and pituitary of the inshore hagfish Eptatretus burgeri to obtain further understanding of the neuroendocrine system of PrRP2. PrRP2-immunoreactive (ir) cell bodies were detected in the infundibular nucleus of hypothalamus (HYinf). PrRP2-ir fibers were restricted around PrRP2-ir cell bodies and were not detected in the dorsal wall of the neurohypophysis compared to the abundant PrRP2-ir fiber distribution in the brain and innervation to the pituitary in other vertebrates. To examine possible reciprocal connections of PrRP2 and other neuropeptides, we further conducted dual-label immunohistochemistry of PrRP2 and the PQRFamide (PQRFa) peptide or corticotropin-releasing hormone (CRH). Reciprocal connections are suggested between PrRP2 and PQRFa neurons as well as between PrRP2 and CRH neurons. The present study demonstrates, for the first time, that PrRP2 is expressed in the brain of inshore hagfish. The restricted distribution of PrRP2-ir fibers in the HYinf suggests that PrRP2 does not directly regulate the pituitary gland, but regulates the function of the HYinf where PQRFa and CRH are expressed. [ABSTRACT FROM AUTHOR]

A neuromodulatory role for dopamine has been reported for magnocellular neuroendocrine cells in the mammalian hypothalamus. We examined its potential role as a local intercellular messenger in the neuroendocrine Dahlgren cell population of the caudal neurosecretory system (CNSS) of the euryhaline flounder Paralichthys olivaceus . In vitro application of dopamine (DA) caused an increase in electrical activity (firing frequency, recorded extracellularly) of Dahlgren cells, recruitment of previously silent cells, together with a greater proportion of cells showing phasic (irregular) activity. The dopamine precursor, levodopa (L-DOPA), also increased firing frequency, cell recruitment and enhanced bursting and tonic activity. The effect of dopamine was blocked by the D1, D5 receptor antagonist SCH23390, but not by the D2, D3, D4 receptor antagonist amisulpride. Transcriptome sequencing revealed that all DA receptors (D1, D2, D3, D4, and D5) were present in the flounder CNSS. However, quantitative RT-PCR revealed that D5 receptor mRNA expression was significantly increased in the CNSS following dopamine superfusion. These findings suggest that dopamine may modulate CNSS activity in vivo , and therefore neurosecretory output, through D5 receptors. [ABSTRACT FROM AUTHOR]

Spexin (SPX), a novel peptide coevolved with the galanin/kisspeptin family, was first identified by bioinformatics prior to its protein purification/functional studies. Its mature peptide is highly conserved among different vertebrate classes. Based on the studies in mammals and fish models, SPX was found to be widely distributed at tissue level, secreted into systemic circulation, identified at notable levels in central nervous system and peripheral tissues, and has been confirmed/implicated in multiple functions in different tissues/organs, suggesting that SPX may serve as a neuroe​ndocrine signal with pleotropic functions. In this article, different isoforms of SPX and their binding with their cognate receptors GalR2 and GalR3, the biological functions of SPX reported in mammals including GI tract movement, energy balance and weight loss, fatty acid uptake, glucose homeostasis, nociception and cardiovascular/renal functions, as well as the recent findings in fish models regarding the role of SPX in reproduction and feeding control will be reviewed with interesting questions for future investigations. [ABSTRACT FROM AUTHOR]

This review analyzes what could be regarded as the “ clandestine organs ” of the endocrine system: the gut microbiome, the immune system, and the stress system. The immune system is very closely related to the endocrine system, with many intertwined processes and signals. Many researchers now consider the microbiome as an ‘organ’ that affects the organism at many different levels. While stress is certainly not an organ, it affects so many processes, including endocrine-related processes, that the stress response system deserved a special section in this review. Understanding the connections, effects, and feedback mechanisms between the different “ clandestine organs ” and the endocrine system will provide us with a better understanding of how an organism functions, as well as reinforce the idea that there are no independent organs or systems, but a complex, interacting network of molecules, cells, tissues, signaling pathways, and mechanisms that constitute an individual. [ABSTRACT FROM AUTHOR]

Differential transfer of maternal testosterone (T) into egg yolk provides a means of adjusting an offspring’s phenotype to ambient environmental conditions. While the environmental and genetic driven variability in yolk T levels is widely described, the underlying mechanisms are poorly understood. Here, we investigated whether neuroendocrine mechanisms controlling ovulatory processes are associated with the regulation of yolk T deposition. Circulatory profiles of luteinizing hormone (LH), T and estradiol levels were analysed during the last 7 h before ovulation in Japanese quail selected for contrasting yolk T concentrations. Moreover, the pituitary responsiveness to a single challenge with gonadotropin releasing hormone (GnRH) was evaluated. High egg T (HET) birds displayed higher concentrations of LH at 3.5 h before ovulation than low egg T (LET) birds while no differences were found around the time of expected ovulation. The pre-ovulatory profile of T and estradiol levels did not differ between LET and HET females but pre-ovulatory plasma T positively correlated with LH concentrations at 6.5 h and 3.5 h before ovulation. The LH response to GnRH did not differ between LET and HET females. Our results demonstrate that the pre-ovulatory LH surge can determine the amount of T transferred into the egg yolk. This link between yolk T deposition and the ovulatory cycle driven variation of reproductive hormones may explain balance between the effects of circulating T on female’s reproductive physiology and yolk T on offspring phenotype. [ABSTRACT FROM AUTHOR]

Several light sensitive receptors have been described in the avian brain that are thought to regulate the reproductive axis independently from the eyes and pineal gland. Recently, our lab has described the presence of three of these photoneuroendocrine systems in the Pekin duck: opsin, opsin 5, & melanopsin. We set out to test the hypothesis that melanopsin receptive neurons are necessary to maintain seasonal reproductive status along with growth and development in the Pekin drake. To accomplish these goals we first investigated 50-week-old Pekin drakes that were housed in the aviary at Hope College under long day length (18 h lights on) conditions in floor pens. To specifically lesion melanopsin-receptive neurons, 3 μl of an anti-melanopsin-saporin conjugate (MSAP, 100 ng/ul) was injected into the lateral ventricle (n = 10). Control drakes were injected with 3 μl of equimolar unconjugated anti-melanopsin and saporin (SAP, n = 10). Reproductive behaviors were analyzed weekly in a test pen with adult hens and MSAP drakes showed a significant (p < 0.01) reduction in reproductive behaviors after week 2. After 5 weeks, drakes were euthanized and body weights were measured, and brains, pituitaries, and testes collected and stored for analyses. Mature MSAP-treated drakes had significantly (p < 0.001) reduced relative teste weights compared to SAP controls. qRT-PCR analyses of hypothalamus showed a significant reduction (p < 0.001) in GnRH and melanopsin mRNA levels, but not opsin 5, vertebrate ancient opsin, or opsin 2 (rhodopsin). Immunocytochemical analyses showed a significant reduction (p < 0.01) in tyrosine hydroxylase-immunoreactivity in the PMM. These data suggest that although blue light alone is not able to maintain testicular function, the blue-light sensitive melanopsin activity is critical to maintain gonadal function. [ABSTRACT FROM AUTHOR]

From an evolutionary point of view, the thymus is a new organ observed for the first time in fish concomitantly with the appearance of adaptive clonotypical immunity. Hormone and neuropeptide expression was demonstrated in different species suggesting a conserved role of these molecules. An integrated evolution of immune and neuroendocrine responses appears to have been realized by means of the re-use of ancestral material, such as neuroendocrine cells and mediators, to create a thymic microenvironment for the maturation and differentiation of T cells. [ABSTRACT FROM AUTHOR]

The article presents an overview of the comparative distribution, structure and functions of the nonapeptide hormones in chordates and non chordates. The review begins with a historical preview of the advent of the concept of neurosecretion and birth of neuroendocrine science, pioneered by the works of E. Scharrer and W. Bargmann. The sections which follow discuss different vertebrate nonapeptides, their distribution, comparison, precursor gene structures and processing, highlighting the major differences in these aspects amidst the conserved features across vertebrates. The vast literature on the anatomical characteristics of the nonapeptide secreting nuclei in the brain and their projections was briefly reviewed in a comparative framework. Recent knowledge on the nonapeptide hormone receptors and their intracellular signaling pathways is discussed and few grey areas which require deeper studies are identified. The sections on the functions and regulation of nonapeptides summarize the huge and ever increasing literature that is available in these areas. The nonapeptides emerge as key homeostatic molecules with complex regulation and several synergistic partners. Lastly, an update of the nonapeptides in non chordates with respect to distribution, site of synthesis, functions and receptors, dealt separately for each phylum, is presented. The non chordate nonapeptides share many similarities with their counterparts in vertebrates, pointing the system to have an ancient origin and to be an important substrate for changes during adaptive evolution. The article concludes projecting the nonapeptides as one of the very first common molecules of the primitive nervous and endocrine systems, which have been retained to maintain homeostatic functions in metazoans; some of which are conserved across the animal kingdom and some are specialized in a group/lineage-specific manner. [ABSTRACT FROM AUTHOR]

• The microstructure of brain and pituitary were detected in Chinese sturgeon. • 46 hypothalamus neuropeptides were dig out from Chinese sturgeon transcriptome data. • Six pituitary hormones (GH, SL, LH, FSH and α-MSH) were detected in Chinese sturgeon. • LH and FSH were secreted by different pituitary cells in Chinese sturgeon. • The gene copies generated in 3R genome duplication were not found in Chinese sturgeon. The hypothalamus and pituitary serve as important neuroendocrine center, which is able to secrete a variety of neuropeptides and hormones to participate in the regulation of reproduction, growth, stress and feeding in fish. Chinese sturgeon is a basal vertebrate lineage fish with a special evolutionary status, but the information on its neuroendocrine system is relatively scarce. Using the transcriptome data on the hypothalamus-pituitary axis of Chinese sturgeon as reference, we found out 46 hypothalamus neuropeptide genes, which were involved in regulation of reproduction, growth, stress and feeding. The results of sequence alignment showed that the neuroendocrine system of Chinese sturgeon evolves slowly, which confirms that Chinese sturgeon is a species with a slow phenotypic evolution rate. In addition, we also isolated six pituitary hormones genes from Chinese sturgeon, including reproductive hormones: follicle-stimulating homone (FSH) and luteinizing hormone (LH), growth-related hormones: growth hormone (GH)/prolactin (PRL)/somatolactin (SL), and stress-related hormone gene: proopiomelanocortin (POMC). Similar to teleost, immunostaining localization analysis in Chinese sturgeon pituitary showed that LH and FSH were located in the pituitary proximal pars distalis, SL was located in the pituitary rostral pars distalis, and POMC was located in the pituitary pars intermedia and pituitary rostral pars distalis. This study will give a contribution to enrich our information on the neuroendocrine system in Chinese sturgeon. [ABSTRACT FROM AUTHOR]

The effect of photo-neuroendocrine system on the thymic (immune) functions is mediated by gonadal steroid and the pineal hormone melatonin. The present study explored the effect of photoperiod on the thymic melatonergic system and its role in protection of thymic T-cells from the testosterone induced seasonal oxidative stress and apoptosis. Exposure to long day-length (LD) was noted to decrease local (thymic) melatonin content and induce oxidative stress and apoptosis in the thymus. Increased peripheral level of testosterone upregulated the androgen receptor expression and, consequently reduced proliferation response of the thymocytes. Short day conditions (SD) however, reversed the effect of LD on the thymic physiology. Low level of testosterone was concomitant with diminished nitro-oxidative stress and decreased expression of redox sensitive factors (NF-κB, p53 and Bax/Bcl-2 ratio) in the thymus. SD retarded activation of caspase-3 resulting in procaspase-3 accumulation. Further, in vitro treatment of thymocytes with AR antagonist flutamide impaired the sensitivity of thymocytes to androgen and reversed the deleterious effects of testosterone on the proliferative and apoptotic responses of thymocytes. Therefore, it can be suggested that thymus derived melatonin protects thymic T-cells from testosterone induced seasonal oxidative stress, apoptosis and also acts as a potent paracrine factor for maintenance of redox status to ensure thymocyte survival. [ABSTRACT FROM AUTHOR]

Across vertebrates, ovulation and sperm release are primarily triggered by the timed surge of luteinizing hormone (LH). These key reproductive events are governed by the action of several brain neuropeptides, pituitary hormones and gonadal steroids which operate to synchronize physiology with behaviour. In amphibians, it has long been recognized that the neuropeptide gonadotropin-releasing hormone (GnRH) has stimulatory effects to induce spawning. Extensive work in teleosts reveals an inhibitory role of dopamine in the GnRH-regulated release of LH. Preliminary evidence suggests that this may be a conserved function in amphibians. Emerging studies are proposing a growing list of modulators beyond GnRH that are involved in the control of spawning including prolactin, kisspeptins, pituitary adenylate cyclase-activating polypeptide, gonadotropin-inhibitory hormone and endocannabinoids. Based on these physiological data, spawning induction methods have been developed to test on selective amphibian species. However, several limitations remain to be investigated to strengthen the evidence for future applications. The current state of knowledge regarding the neuroendocrine control of spawning in amphibians will be reviewed in detail, the elements of which will have wide implications towards the captive breeding of endangered amphibian species for conservation. [ABSTRACT FROM AUTHOR]

Zebrafish ( Danio rerio ) is an emerging model for integrative physiological research. In this mini-review, we discuss recent advances in the neuroendocrine control of ionic balance in this species, and identify current knowledge gaps and issues that would benefit from further investigation. Zebrafish inhabit a hypo-ionic environment and therefore are challenged by a continual loss of ions to the water. To maintain ionic homeostasis, they must actively take up ions from the water and reduce passive ion loss. The adult gill or the skin of larvae are the primary sites of ionic regulation. Current models for the uptake of major ions in zebrafish incorporate at least three types of ion transporting cells (also called ionocytes); H + -ATPase-rich cells for Na + uptake, Na + /K + -ATPase-rich cells for Ca 2+ uptake, and Na + /Cl − -cotransporter expressing cells for both Na + and Cl − uptake. The precise molecular mechanisms regulating the paracellular loss of ions remain largely unknown. However, epithelial tight junction proteins, including claudins, are thought to play a critical role in reducing ion losses to the surrounding water. Using the zebrafish model, several key neuroendocrine factors were identified as regulators of epithelial ion movement, including the catecholamines (adrenaline and noradrenaline), cortisol, the renin-angiotensin system, parathyroid hormone and prolactin. Increasing evidence also suggests that gasotransmitters, such as H 2 S, are involved in regulating ion uptake. [ABSTRACT FROM AUTHOR]

Male-typical reproductive behaviors vary greatly between different species of fishes with androgens playing a variety of roles that appear especially important in the gonochorist cypriniform fishes. The goldfish is an important model for the cypriniformes and while it is clear that male goldfish are fully feminized by prostaglandin F 2α (PGF 2α ), it is not clear whether females will exhibit normal levels of male-typical reproductive behaviors as well as olfactory function when treated with androgens. To answer this question, we exposed sexually-regressed adult female goldfish to several types of androgen and monitored their tendencies to court (inspect females) and mate (spawn, or attempt to release gametes) while monitoring their olfactory sensitivity until changes in these attributes were maximized. Untreated adult males (intact) were included to determine the extent of masculinization. Treatments included the natural androgens, 11-ketotestosterone and testosterone (KT and T), administered via capsules (KT + T-implanted fish); the artificial androgen, methyltestosterone (MT), administered via capsules (MT-C); and MT administered in the fishes’ water (MT-B). Male-typical olfactory sensitivity to a pheromone (15keto-PGF 2α ) increased in all androgen-treated groups and by week 6 was fully equivalent to that of males. Male-typical courtship behavior increased in all androgen-treated groups although slowly, and only MT-B females came to exhibit levels equivalent to those of males after 18 weeks. In contrast, male-typical mating activity increased only slightly, with MT-B females reaching levels one-third that of males after 30 weeks. We conclude that while androgens fully masculinize olfactory sensitivity and courtship behavior in goldfish, mating behavior is controlled by a different neuroendocrine mechanism(s) that has yet to be fully elucidated. [ABSTRACT FROM AUTHOR]

Ascidians are the closest phylogenetic neighbors to vertebrates and are believed to conserve the evolutionary origin in chordates of the endocrine, neuroendocrine, and nervous systems involving neuropeptides and peptide hormones. Ciona intestinalis harbors various homologs or prototypes of vertebrate neuropeptides and peptide hormones including gonadotropin-releasing hormones (GnRHs), tachykinins (TKs), and calcitonin, as well as Ciona -specific neuropeptides such as Ciona vasopressin, LF, and YFV/L peptides. Moreover, molecular and functional studies on Ciona tachykinin (Ci-TK) have revealed the novel molecular mechanism of inducing oocyte growth via up-regulation of vitellogenesis-associated protease activity, which is expected to be conserved in vertebrates. Furthermore, a series of studies on Ciona GnRH receptor paralogs have verified the species-specific regulation of GnRHergic signaling including unique signaling control via heterodimerization among multiple GnRH receptors. These findings confirm the remarkable significance of ascidians in investigations of the evolutionary processes of the peptidergic systems in chordates, leading to the promising advance in the research on Ciona peptides in the next stage based on the recent development of emerging technologies including genome-editing techniques, peptidomics-based multi-color staining, machine-learning prediction, and next-generation sequencing. These technologies and bioinformatic integration of the resultant “multi-omics” data will provide unprecedented insights into the comprehensive understanding of molecular and functional regulatory mechanisms of the Ciona peptides, and will eventually enable the exploration of both conserved and diversified endocrine, neuroendocrine, and nervous systems in the evolutionary lineage of chordates. [ABSTRACT FROM AUTHOR]

Since its first identification in quail 15 years ago, gonadotropin inhibitory hormone (GnIH) has become a central regulator of reproduction in avian species. In this review, we have revisited our original model published in 2009 to incorporate recent experimental evidence suggesting that GnIH acts as a molecular switch during the integration of multiple external and internal cues that allow sexual maturation to proceed in chickens. Furthermore, we discuss the regulation of a dual inhibitory/stimulatory control of the hypothalamo-pituitary–gonadal axis involving the interaction between GnIH and gonadotropin releasing hormone (GnRH). Finally, beyond seasonality, we also propose that GnIH along with this dual control may be responsible for the circadian control of ovulation in chickens, allowing eggs to be laid in a synchronized manner. [ABSTRACT FROM AUTHOR]

CART (cocaine- and amphetamine-regulated transcript) is a peptide with neurotransmitter and neuroendocrine functions with several key roles, both centrally and peripherally. In mammals there is a single gene that produces two alternatively spliced variants in rat and a single transcript in human but in teleosts multiple genes have been found. In the present study we report the existence of seven transcripts in Senegalese sole and characterize their sequences and phylogenetic relationships, as well as their expression patterns in the brain and peripheral tissues, and in response to feeding. Both cart2a and cart4 showed a ubiquitous expression in the brain, while cart1a , cart1b and cart3a were similarly expressed and had higher transcript levels in the mesencephalon, followed by the diencephalon. On the other hand, cart2b showed a main expression in the olfactory bulbs, and cart3b was predominantly expressed in the spinal cord. The expression profile in peripheral tissues differed substantially between cart ’s, even between more recently duplicated genes. Collectively, all the tissues examined, except the muscle, express at least one of the different cart ’s, although the highest transcript levels were found in the brain, gonads (ovary and testis) and, in some cases, eye and kidney. Concerning the feeding response, only brain cart1a , cart2a and cart4 showed a significant postprandial regulation, although future studies are necessary to assess potential confounding effects of stress imposed by the force feeding technique employed. Senegalese sole exhibits the highest number of cart genes reported to date in a vertebrate species. Their differential expression patterns and feeding regulation suggest that multiple cart genes, resulting from at least 3 rounds of whole genome duplication, have been retained in fish genomes through subfunctionalization, or possibly even through neofunctionalization. [ABSTRACT FROM AUTHOR]

Neurokinin B (NKB) is a member of the tackykinin ( TAC ) family known to play a critical role in the neuroendocrine regulation of reproduction in mammals. However, its biological functions in teleosts are less clear. The aim of this study was to determine the role of NKB in fish reproduction using goldfish as a model. Two transcripts, TAC3a and TAC3b , which encode several NKBs, including NKBa-13, NKBa-10, NKBb-13, and NKBb-11, were cloned. Phylogenetic analysis revealed that NKBa-10 and NKBb-11 are closely related to mammalian NKB, while NKB-13s are more conserved in teleosts. Quantitative real-time PCR analyses in various tissues showed that TAC3a and TAC3b mRNAs were mainly expressed in the brain. In situ hybridization further detected TAC3a and TAC3b mRNAs in several regions of the brain known to be involved in the regulation of reproduction and metabolism, as well as in the neurohypophysis of the pituitary. To investigate the potential role of NKBs in reproduction, goldfish were injected intraperitoneally with synthetic NKBa-13, -10, NKBb-13, or -11 peptides and the mRNA levels of hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary gonadotropin subunits were measured. NKBa-13, -10, or NKBb-13, but not -11, significantly increased hypothalamic salmon GnRH and pituitary FSHβ and LHβ mRNA levels in both female and male goldfish. Finally, ovariectomy increased, while estradiol replacement reduced, TAC3a mRNA levels without affecting TAC3b expression in the hypothalamus. These data suggest that NKBa-13, -10, and NKBb-13 play a role in mediating the estrogen negative feedback regulation of gonadotropins. [ABSTRACT FROM AUTHOR]

Abstract: Sea lampreys are anadromous and semelparous, i.e., they spawn only once in their lifetime, after which they die. Sexual maturation is thus a synchronized process coordinated with the life stages of the lamprey. Recently, a novel gonadotropin-releasing hormone, lamprey GnRH-II (lGnRH-II), was identified in lampreys and suggested to have a hypothalamic role in reproduction (). To further understand the role of lGnRH-II, changes in ovarian morphology, brain gonadotropin-releasing hormone (lGnRH-I, -II, and -III), and plasma estradiol were examined during the final two months of the reproductive season of adult male and female sea lamprey. The results showed significant correlations between water temperature, fluctuation of brain GnRHs, plasma estradiol and reproductive stages during this time. In males, lGnRH-I concentration increased early in the season, peaked, then declined with a subsequent increase with the final maturational stages. In comparison, lGnRH-II and -III concentrations were also elevated early in the season in males, dropped and then peaked in mid-season with a subsequent decline of lGnRH-II or increase of lGnRH-III at spermiation. In females, lGnRH-III concentration peaked in mid-season with a drop at ovulation while lGnRH-I remained unchanged during the season. In contrast, lGnRH-II concentrations in females were elevated at the beginning of the season and then dropped and remained low during the rest of the season. In summary, these data provide evidence that there are seasonal and differential changes of the three GnRHs during this final reproductive period suggesting specific roles for each of the GnRHs in male and female reproduction. [ABSTRACT FROM AUTHOR]

Abstract: This review aims at synthesizing the most relevant information regarding the neuroendocrine circuits controlling reproduction, mainly gonadotropin release, in teleost fish. In teleosts, the pituitary receives a more or less direct innervation by neurons sending projections to the vicinity of the pituitary gonadotrophs. Among the neurotransmitters and neuropeptides released by these nerve endings are gonadotrophin-releasing hormones (GnRH) and dopamine, acting as stimulatory and inhibitory factors (in many but not all fish) on the liberation of LH and to a lesser extent that of FSH. The activity of the corresponding neurons depends on a complex interplay between external and internal factors that will ultimately influence the triggering of puberty and sexual maturation. Among these factors are sex steroids and other peripheral hormones and growth factors, but little is known regarding their targets. However, very recently a new actor has entered the field of reproductive physiology. KiSS1, first known as a tumor suppressor called metastin, and its receptor GPR54, are now central to the regulation of GnRH, and consequently LH and FSH secretion in mammals. The KiSS system is notably viewed as instrumental in integrating both environmental cues and metabolic signals and passing this information onto the reproductive axis. In fish, there are two KiSS genes, KiSS1 and KiSS2, expressed in neurons of the preoptic area and mediobasal hypothalamus. Pionneer studies indicate that KiSS and GPR54 expression seem to be activated at puberty. Although precise information as to the physiological effects of KiSS1 in fish, notably on GnRH neurons and gonadotropin release, is still limited, KiSS neurons may emerge as the “gatekeeper” of puberty and reproduction in fish as in mammals. [Copyright &y& Elsevier]

• Zebrafish tac3a −/−, tac3b −/− and tac3a −/−; tac3b −/− mutant lines were established. • Knockout of tac3 genes did not impair the zebrafish reproduction. • Compensation mechanisms were activated to stimulate the reproductive axis. Neurokinin B (NKB) plays a pivotal role in the regulation of reproduction in vertebrates. However, whether this neuropeptide is dispensable for reproduction in teleosts remains unknown. In order to reveal its authentic functions in fish, in this study, two tachykinin 3 (tac3) genes encoding Nkbs were functional mutated in zebrafish using the Transcription Activator-like Effector Nucleases (TALEN) technology. We established tac3a −/−, tac3b −/− and tac3a −/−; tac3b −/− mutant lines, and investigated their reproductive performance and ontogeny. According to our study, spermatogenesis and folliculogenesis were not impaired in tac3a −/−, tac3b −/− and tac3a −/−; tac3b −/− mutant lines, but changes in the expression of genes related to reproductive axis were observed after loss of Tac3, suggesting that possible compensatory response was activated to maintained the reproductive function in zebrafish. In summary, our results indicate that mutation of tac3 genes do not disrupt the reproduction in zebrafish unlike in mammals, revealing the plasticity of reproductive neuroendocrine system in the brain of zebrafish. [ABSTRACT FROM AUTHOR]

Several neurohormonal peptides of the gastrointestinal system of fish have been revealed by immunohistochemical methods. Among salmonids, the rainbow trout, Oncorhynchus mykiss (Walbaum) is the most studied species, whereas the informations about other species of the taxonomic group are lacking. The regional distribution and relative densities of cells belonging to the neuroendocrine system have been in this paper demonstrated in the gut of the brown trout, Salmo trutta Linnaeus. In the gastric mucosa, endocrine cells were detected, which were immunoreactive to bombesin-, gastrin-, and secretin-antisera. Endocrine cells containing gastrin-, bombesin-, cholecystokinin-8-, glucagon-, and leptin-like immunoreactivities were present in the pyloric caeca and intestine. The pancreatic endocrine islets contained glucagon-, and, possibly, secretin-like-immunoreactive endocrine cells, as well as a contingent of galanin-like-immunoreactive nerve fibres. The exocrine pancreatic parenchyma showed bombesin-like-immunoreactive nerve fibres. Within the tested regulatory peptides, bombesin and leptin were observed in both endocrine cells and nerve cell bodies and fibres. Leptin was in addition detected in epithelial cells of the gastric glands. In the brown trout we have never observed any immunoreactivity to the VIP antiserum (either in the stomach or in the intestine). Some special structural patterns (in particular those ones related to galanin- and leptin-immunohistochemical data) have thus been detected for the first time in the brown trout, and provide further data for a better knowledge of gut morpho-functional aspects in this economically important fish. [Copyright &y& Elsevier]

• The gene expression patterns were examined for hypothalamic neuropeptides and pituitary hormones in wild tiger puffer. • The expression of the genes for three GnRHs, GnIH, GnIH-R, FSHβ and LHβ were extensively activated in the mature fish. • The expression levels of the GnRH/GnIH/GTH system were drastically decreased in the post-ovulatory females. Tiger puffer, Takifugu rubripes , a commercially important long-distance migratory fish, return to specific spawning grounds for reproduction. To clarify reproductive neuroendocrine system of the tiger puffer, the changes in the expression levels of the genes encoding three gonadotropin-releasing hormones (GnRHs), gonadotropin-inhibitory hormone (GnIH), GnIH receptor (GnIH-R), kisspeptin and kisspeptin receptor in the brain and gonadotropin (GTH) subunits, growth hormone (GH) and prolactin (PRL) in the pituitary were examined in the tiger puffer captured in the wild at different reproductive stages, namely immature and mature fish of both sexes, and post-ovulatory females that were obtained by hormonal treatment. The amounts of three gnrh mRNAs, gnih , gnih-r , fshb and lhb were substantially increased in the mature fish compared to the immature fish, especially in the females, and these augmented expressions were drastically decreased in the post-ovulatory females. gh expression showed a slight increase in the mature males. In contrast, kiss2 , kiss2r and prl did not show significant changes in the males but significantly decreased in the post-ovulatory females. The present results demonstrate the expression dynamics of the hypothalamo-pituitary-gonadal axis genes associated with the reproductive conditions and the possible involvement of the GnRH/GnIH/GTH system in the regulation of the sexual maturation and spawning in the wild tiger puffer. [ABSTRACT FROM AUTHOR]

• Stress and reproductive functions interact negatively or positively throughout teleost life cycles. • Corticotropic and gonadotropic axes present some anatomo-functional and molecular specificities in teleosts. • Interactions between corticotropic and gonadotropic actors occur at all levels from brain, pituitary to gonads and interrenals. Stress and reproduction are both essential functions for vertebrate survival, ensuring on one side adaptative responses to environmental changes and potential life threats, and on the other side production of progeny. With more than 25,000 species, teleosts constitute the largest group of extant vertebrates, and exhibit a large diversity of life cycles, environmental conditions and regulatory processes. Interactions between stress and reproduction are a growing concern both for conservation of fish biodiversity in the frame of global changes and for the development of sustainability of aquaculture including fish welfare. In teleosts, as in other vertebrates, adverse effects of stress on reproduction have been largely documented and will be shortly overviewed. Unexpectedly, stress notably via cortisol, may also facilitate reproductive function in some teleost species in relation to their peculiar life cyles and this review will provide some examples. Our review will then mainly address the neuroendocrine axes involved in the control of stress and reproduction, namely the corticotropic and gonadotropic axes, as well as their interactions. After reporting some anatomo-functional specificities of the neuroendocrine systems in teleosts, we will describe the major actors of the corticotropic and gonadotropic axes at the brain-pituitary-peripheral glands (interrenals and gonads) levels, with a special focus on the impact of teleost-specific whole genome duplication (3R) on the number of paralogs and their potential differential functions. We will finally review the current knowledge on the neuroendocrine mechanisms of the various interactions between stress and reproduction at different levels of the two axes in teleosts in a comparative and evolutionary perspective. [ABSTRACT FROM AUTHOR]

• Secretoneurin is a conserved vertebrate neuropeptide derived from enzymatic processing of secretogranin-2. • Secretoneurin exhibits multiple biological activities in neurogenesis and neuroinflammation. • Considerable evidence now indicates the secretogranin-2/Secretoneurin plays a fundamental stimulatory role in reproduction. Secretogranin-2 (SCG2) is a large precursor protein that is processed into several potentially bioactive peptides, with the 30–43 amino acid central domain called secretoneurin (SN) being clearly evolutionary conserved in vertebrates. Secretoneurin exerts a diverse array of biological functions including regulating nervous, endocrine, and immune systems in part due to its wide tissue distribution. Expressed in some neuroendocrine neurons and pituitary cells, SN is a stimulator of the synthesis and release of luteinizing hormone from both goldfish pituitary cells and the mouse LβT2 cell line. Neuroendocrine, paracrine and autocrine signaling pathways for the stimulation of luteinizing hormone release indicate hormone-like activities to regulate reproduction. Mutation of the scg2a and scg2b genes using TALENs in zebrafish reduces sexual behavior, ovulation, oviposition, and fertility. A single injection of the SNa peptide enhanced reproductive outcomes in scg2a / scg2b double mutant zebrafish. Evidence in goldfish suggests a new role for SN to stimulate food intake by actions on other feeding-related neuropeptides. Expression and regulation of the Scg2a precursor mRNA in goldfish gut also supports a role in feeding. In rodent models, SN has trophic-like properties promoting both neuroprotection and neuronal plasticity and has chemoattractant properties that regulate neuroinflammation. Data obtained from several cellular models suggest that SN binds to and activates a G-protein coupled receptor (GPCR), but a bona fide SN receptor protein needs to be identified. Other signaling pathways for SN have been reported which provides alternatives to the GPCR hypothesis. These include AMP-activated protein kinase (AMPK), extracellular signal-regulated kinases (ERK), mitogen-activated protein kinase (MAPK) and calcium/calmodulin-dependent protein kinase II in cardiomyocytes, phosphatidylinositol 3-kinase (PI3K) and Akt/Protein Kinase B (AKT, and MAPK in endothelial cells and Janus kinase 2/signal transducer and activator of transcription protein (JAK2-STAT) signaling in neurons. Some studies in cardiac cells provide evidence for cellular internalization of SN by an unknown mechanism. Many of the biological functions of SN remain to be fully characterized, which could lead to new and exciting applications. [ABSTRACT FROM AUTHOR]

• How the elevated glucose return to basal level remains unclear in crustaceans. • This study characterized the Mr-ILP gene and investigated its function. • Mr-ILP contributes to oligosaccharide and polysaccharide accumulation from glucose. • The expression of CHH is regulated by Mr-ILP and negative feedback mechanism. • Glycolysis play an important role in lowering glucose concentration. This study identified an insulin-like peptide (ILP) in Macrobrachium rosenbergii termed Mr-ILP and further investigated its function through glucose injection and RNAi. With the analysis of five other glucose metabolism related genes, this study shed light on the molecular mechanism of carbohydrate metabolism in crustaceans. Mr-ILP shared the typical skeleton with six conserved cysteine and mainly expressed in neuroendocrine system. In M. rosenbergii , the elevated hemolymph glucose concentration after glucose injection returned to basal levels in short time, implying an efficient regulatory system in carbohydrate metabolism. Hyperglycemic related genes answered the elevated hemolymph glucose concentration quickly with significant decreased expression level, while Mr-ILP showed delayed response. Instead, glycolysis increased after glucose injection, which indicated glycolysis might play an important role in lowering the abnormally high glucose level. In vivo silencing of Mr-ILP , by injecting the prawns with double-stranded RNA (dsRNA) for 21 days reduced its expression by approximately 75%. Accordingly, glycogen synthase decreased and the trehalose and glycogen level in the hepatopancreas were significantly reduced, indicating the function of Mr-ILP in oligosaccharide and polysaccharide accumulation. When Mr-ILP was silenced, the expression of hyperglycemic related genes were enhanced, but the hemolymph glucose level was not elevated significantly, which might attribute to the increased glycolysis to keep a balanced glucose level in hemolymph. [ABSTRACT FROM AUTHOR]

• The role of the microbiome in regulating the host endocrine system is reviewed. • Bi-directional action regulates the microbiome-endocrine axis. • Endocrine disrupting chemical severity is influenced by microbial transformations. • Multi-dimensional approaches are needed to examine the microbiome-endocrine axis. The microbiome regulates endocrine systems and influences many aspects of hormone signaling. Using examples from different animal taxa, we highlight the state of the science in microbiome research as it relates to endocrinology and endocrine disruption research. Using a comparative approach discussing fish, birds, and mammals, we demonstrate the bidirectional interaction between microbiota and hormone systems, presenting concepts that include (1) gastrointestinal microbiome regulation of the neuroendocrine feeding axis; (2) stress hormones and microbial communities; (3) the role of site-specific microbiota in animal reproduction; (4) microbiome effects on the neuroendocrine systems and behavior; and (5) novel mechanisms of endocrine disruption through the microbiome. This mini-review demonstrates that hormones can directly affect the richness and diversity of microbiota and conversely, microbiota can influence hormone production and mediate their functions in animals. In addition, microbiota can influence the action of a diverse range of neurotransmitters and neuropeptides in the central nervous system, which can lead to behavioral disruptions. As many animals have species-specific reproductive behaviors, it is important to understand how shifts in the microbiota relate to these complex interactions between sexes. This is especially important for captive animals on specialized diets, and there are significant implications for microbiome research in conservation and reproductive biology. For example, microbial metabolites may modify motility of gametes or modulate hormone-receptor interactions in reproductive tissues. Thus, efforts to incorporate metabolomics into the science of microbiome-endocrine relationships, both those produced by the host and those generated from microbial metabolism, are increasingly needed. These concepts have fostered an exciting emerging era in comparative endocrinology. [ABSTRACT FROM AUTHOR]

• Food-restricted birds have smaller testes but unaltered plasma testosterone. • Baseline plasma luteinizing hormone is marginally lowered by food restriction. • Food restriction enhances the secretory capacity of gonadotropin-releasing hormone. Seasonal activation of the vertebrate hypothalamic-pituitary-gonadal (HPG) axis and gonadal development is initiated by gonadotropin-releasing hormone-I (GnRH) release from the hypothalamus. In photoperiodic species, the consistent annual change in photoperiod is the primary environmental signal affecting GnRH cell activity, including changes in the synthesis and secretion of this neuropeptide. Non-photoperiodic environmental cues such as energy availability also influence HPG axis activity, but the mechanisms mediating this influence, in particular on the GnRH system, are unclear. Understanding how the neuroendocrine system integrates environmental information is critical in determining the plasticity and adaptability of physiological responses to changing environments. The primary objective of this study was to investigate GnRH-mediated changes in HPG axis activity and gonadal development in response to energy availability in a wild bird. We hypothesized that negative energy balance inhibits HPG axis activity by affecting GnRH secretion. Moderate food restriction for several weeks in male house finches, Haemorhous mexicanus, decreased body condition and inhibited photoinduced testicular growth compared to birds fed ad libitum. Food restriction did not affect plasma luteinizing hormone (LH; a correlate of GnRH release) or plasma testosterone, but it enhanced the plasma LH response to an injection of the glutamatergic agonist, N-methyl-D-aspartate (NMDA). Thus, food restriction may decrease photoinduced HPG axis activation by acting centrally, in particular by attenuating the release of accumulated GnRH stores. [ABSTRACT FROM AUTHOR]