History of the Development of Knowledge about the Neuroendocrine Control of Ovulation-Recent Knowledge on the Molecular Background.

The physiology of reproduction has been of interest to researchers for centuries. The purpose of this work is to review the development of our knowledge on the neuroendocrine background of the regulation of ovulation. We first describe the development of the pituitary gland, the structure of the median eminence (ME), the connection between the hypothalamus and the pituitary gland, the ovarian and pituitary hormones involved in ovulation, and the pituitary cell composition. We recall the pioneer physiological and morphological investigations that drove development forward. The description of the supraoptic-paraventricular magnocellular and tuberoinfundibular parvocellular systems and recognizing the role of the hypophysiotropic area were major milestones in understanding the anatomical and physiological basis of reproduction. The discovery of releasing and inhibiting hormones, the significance of pulse and surge generators, the pulsatile secretion of the gonadotropin-releasing hormone (GnRH), and the subsequent pulsatility of luteinizing (LH) and follicle-stimulating hormones (FSH) in the human reproductive physiology were truly transformative. The roles of three critical neuropeptides, kisspeptin (KP), neurokinin B (NKB), and dynorphin (Dy), were also identified. This review also touches on the endocrine background of human infertility and assisted fertilization.

A brief and updated introduction to the neuroendocrine system of crustaceans.

The neuroendocrine system of crustaceans is complex and regulates many processes, such as development, growth, reproduction, osmoregulation, behavior, and metabolism. Once stimulated, crustaceans' neuroendocrine tissues modulate the release of monoamines, ecdysteroids, and neuropeptides that can act as hormones or neurotransmitters. Over a few decades, research has unraveled some mechanisms governing these processes, substantially contributing to understanding crustacean physiology. More aspects of crustacean neuroendocrinology are being comprehended with molecular biology, transcriptome, and genomics analyses. Hence, these studies will also significantly enhance the ability to cultivate decapods, such as crabs and shrimps, used as human food sources. In this review, current knowledge on crustacean endocrinology is updated with new findings about crustacean hormones, focusing mainly on the main neuroendocrine organs and their hormones and the effects of these molecules regulating metabolism, growth, reproduction, and color adaptation. New evidence about vertebrate-type hormones found in crustaceans is included and discussed. Finally, this review may assist in understanding how the emerging chemicals of environmental concern can potentially impair and disrupt crustacean's endocrine functions and their physiology.

The olfactory bulb: A neuroendocrine spotlight on feeding and metabolism.

Olfaction is the most ancient sense and is needed for food-seeking, danger protection, mating and survival. It is often the first sensory modality to perceive changes in the external environment, before sight, taste or sound. Odour molecules activate olfactory sensory neurons that reside on the olfactory epithelium in the nasal cavity, which transmits this odour-specific information to the olfactory bulb (OB), where it is relayed to higher brain regions involved in olfactory perception and behaviour. Besides odour processing, recent studies suggest that the OB extends its function into the regulation of food intake and energy balance. Furthermore, numerous hormone receptors associated with appetite and metabolism are expressed within the OB, suggesting a neuroendocrine role outside the hypothalamus. Olfactory cues are important to promote food preparatory behaviours and consumption, such as enhancing appetite and salivation. In addition, altered metabolism or energy state (fasting, satiety and overnutrition) can change olfactory processing and perception. Similarly, various animal models and human pathologies indicate a strong link between olfactory impairment and metabolic dysfunction. Therefore, understanding the nature of this reciprocal relationship is critical to understand how olfactory or metabolic disorders arise. This present review elaborates on the connection between olfaction, feeding behaviour and metabolism and will shed light on the neuroendocrine role of the OB as an interface between the external and internal environments. Elucidating the specific mechanisms by which olfactory signals are integrated and translated into metabolic responses holds promise for the development of targeted therapeutic strategies and interventions aimed at modulating appetite and promoting metabolic health.

Neural thyroid hormone metabolism integrates seasonal changes in environmental temperature with the neuroendocrine reproductive axis.

We asked if environmental temperature alters thyroid hormone metabolism within the hypothalamus, thereby providing a neuroendocrine mechanism by which temperature could be integrated with photoperiod to regulate seasonal rhythms. We used immunohistochemistry to assess the effects of low-temperature winter dormancy at 4 °C or 12 °C on thyroid-stimulating hormone (TSH) within the infundibulum of the pituitary as well as deiodinase 2 (Dio2) and 3 (Dio3) within the hypothalamus of red-sided garter snakes (Thamnophis sirtalis). Both the duration and, in males, magnitude of low-temperature dormancy altered deiodinase immunoreactivity within the hypothalamus, increasing the area of Dio2-immunoreactivity in males and females and decreasing the number of Dio3-immunoreactive cells in males after 8-16 weeks. Reciprocal changes in Dio2/3 favor the accumulation of triiodothyronine within the hypothalamus. Whether TSH mediates these effects requires further study, as significant changes in TSH-immunoreactive cell number were not observed. Temporal changes in deiodinase immunoreactivity coincided with an increase in the proportion of males exhibiting courtship behavior as well as changes in the temporal pattern of courtship behavior after emergence. Our findings mirror those of previous studies, in which males require low-temperature exposure for at least 8 weeks before significant changes in gonadotropin-releasing hormone immunoreactivity and sex steroid hormones are observed. Collectively, these data provide evidence that the neuroendocrine pathway regulating the reproductive axis via thyroid hormone metabolism is capable of transducing temperature information. Because all vertebrates can potentially use temperature as a supplementary cue, these results are broadly applicable to understanding how environment-organism interactions mediate seasonally adaptive responses.

The neuroendocrine and endocrine systems in insect - Historical perspective and overview.

A complex cascade of events leads to the initiation and maintenance of a behavioral act in response to both internally and externally derived stimuli. These events are part of a transition of the animal into a new behavioral state, coordinated by chemicals that bias tissues and organs towards a new functional state of the animal. This form of integration is defined by the neuroendocrine (or neurosecretory) system and the endocrine system that release neurohormones or hormones, respectively. Here we describe the classical neuroendocrine and endocrine systems in insects to provide an historic perspective and overview of how neurohormones and hormones support plasticity in behavioral expression. Additionally, we describe peripheral tissues such as the midgut, epitracheal glands, and ovaries, which, whilst not necessarily being endocrine glands in the pure sense of the term, do produce and release hormones, thereby providing even more flexibility for inter-organ communication and regulation.

The excitatory effect of 5-HT1A and 5-HT2B receptors on the caudal neurosecretory system Dahlgren cells in olive flounder, Paralichthys olivaceus.

The neurotransmitter 5-hydroxytryptamine (5-HT, serotonin) plays an essential role in the regulation of neural activity via multiple receptors. Here, we investigated the functional role of serotoninergic input on the Dahlgren cell population in the caudal neurosecretory system (CNSS) of olive flounder. In this study, the effect of 5-HT on the firing activity of Dahlgren cells was explored in terms of changes in firing frequency and firing pattern using multicellular recording electrophysiology ex vivo, and the role of several 5-HT receptor subtypes in the regulation was determined. The results revealed that 5-HT increased the firing frequency in a concentration-dependent manner and altered the firing pattern of Dahlgren cells. The effect of 5-HT on the firing activity of Dahlgren cells was mediated through the 5-HT1A and 5-HT2B receptors, selective agonists of both receptors effectively increased the firing frequency of Dahlgren cells, and selective receptor antagonists could also effectively inhibit the increase in firing frequency caused by 5-HT. In addition, the mRNA levels of major signaling pathway-related genes, ion channels, and major secretion hormone genes were significantly upregulated in CNSS after treatment with 5-HT. These findings demonstrate that 5-HT acts as an excitatory neuromodulator on Dahlgren cells and enhances neuroendocrine activity in CNSS.

Neuroendocrine mechanisms contributing to the coevolution of sociality and communication.

Communication is inherently social, so signaling systems should evolve with social systems. The 'social complexity hypothesis' posits that social complexity necessitates communicative complexity and is generally supported in vocalizing mammals. This hypothesis, however, has seldom been tested outside the acoustic modality, and comparisons across studies are confounded by varying definitions of complexity. Moreover, proximate mechanisms underlying coevolution of sociality and communication remain largely unexamined. In this review, we argue that to uncover how sociality and communication coevolve, we need to examine variation in the neuroendocrine mechanisms that coregulate social behavior and signal production and perception. Specifically, we focus on steroid hormones, monoamines, and nonapeptides, which modulate both social behavior and sensorimotor circuits and are likely targets of selection during social evolution. Lastly, we highlight weakly electric fishes as an ideal system in which to comparatively address the proximate mechanisms underlying relationships between social and signal diversity in a novel modality.

Magnetic Resonance Imaging, a New Tool for Neuroendocrine Research in Sheep.

Magnetic resonance imaging (MRI) brain analysis is used in rodents and for clinical investigation in humans, and it becomes also possible now for large animal models studies. Specific facilities are available with clinical scanners and benefit to neuroendocrine investigations in sheep. Sheep has a large gyrencephalic brain and its organization is very similar to primates and human, and among physiological regulations, oestrous cycle of the ewes is similar to women. Therefore, this animal is a good model for preclinical researches using MRI, as illustrated with steroids impact on the brain. New data were obtained concerning the effect of sexual steroids on neuronal networks involved in the control of reproduction and in the influence of sexual steroids on cognition. In addition to the importance of such data for understanding the role of these hormones on brain functions, they give new insights to consider the sheep as a powerful model for preclinical studies in the field of neuroendocrinology. These points are discussed in this short review.

Neuronal regulation of B-cell immunity: Anticipatory immune posturing?

The brain may sense, evaluate, modulate, and intervene in the operation of immune system, which would otherwise function autonomously in defense against pathogens. Antibody-mediated immunity is one arm of adaptive immunity that may achieve sterilizing protection against infection. Lymphoid organs are densely innervated. Immune cells supporting the antigen-specific antibody response express receptors for neurotransmitters and glucocorticoid hormones, and they are subjected to collective regulation by the neuroendocrine and the autonomic nervous system. Emerging evidence reveals a brain-spleen axis that regulates antigen-specific B cell responses and antibody-mediated immunity. In this article, we provide a synthesis of those studies as pertinent to neuronal regulation of B cell responses in secondary lymphoid organs. We propose the concept of defensive immune posturing as a brain-initiated top-down reaction in anticipation of potential tissue injury that requires immune protection.

Synaptic control of rat magnocellular neurosecretory cells by warm-sensing neurons in the organum vasculosum lamina terminalis.

Increases in core body temperature cause secretion of vasopressin (vasopressin, antidiuretic hormone) to promote water reabsorption and blunt water losses incurred through homeostatic evaporative cooling. Subtypes of transient receptor potential vanilloid (Trpv) channels have been shown to contribute to the intrinsic regulation of vasopressin-releasing magnocellular neurosecretory cells (MNCs) in the supraoptic nucleus (SON) and paraventricular nucleus (PVN). However, MNCs in vivo can also be excited by local heating of the adjacent preoptic area, indicating they receive thermosensory information from other areas. Here, we investigated whether neurons in the organum vasculosum lamina terminalis (OVLT) contribute to this process using in vitro electrophysiological approaches in male rats. We found that the majority of OVLT neurons are thermosensitive in the physiological range (36-39°C) and that this property is retained under conditions blocking synaptic transmission. A subset of these neurons could be antidromically activated by electrical stimulation in the SON. Whole cell recordings from SON MNCs revealed that heating significantly increases the rate of spontaneous excitatory postsynaptic currents (sEPCSs), and that this response is abolished by lesions targeting the OVLT, but not by bilateral lesions placed in the adjacent preoptic area. Finally, local heating of the OVLT caused a significant excitation of MNCs in the absence of temperature changes in the SON, and this effect was blocked by inhibitors of ionotropic glutamate receptors. These findings indicate that the OVLT serves as an important thermosensory nucleus and contributes to the activation of MNCs during physiological heating.

Molecular Mechanisms Underlying Stress Response and Resilience.

A variety of stressors induce various physiological responses by modulating sympathetic, neuroendocrine, and behavioral systems [...].

Prenatal Pollutant Exposures and Hypothalamic Development: Early Life Disruption of Metabolic Programming.

Environmental contaminants in ambient air pollution pose a serious risk to long-term metabolic health. Strong evidence shows that prenatal exposure to pollutants can significantly increase the risk of Type II Diabetes (T2DM) in children and all ethnicities, even without the prevalence of obesity. The central nervous system (CNS) is critical in regulating whole-body metabolism. Within the CNS, the hypothalamus lies at the intersection of the neuroendocrine and autonomic systems and is primarily responsible for the regulation of energy homeostasis and satiety signals. The hypothalamus is particularly sensitive to insults during early neurodevelopmental periods and may be susceptible to alterations in the formation of neural metabolic circuitry. Although the precise molecular mechanism is not yet defined, alterations in hypothalamic developmental circuits may represent a leading cause of impaired metabolic programming. In this review, we present the current knowledge on the links between prenatal pollutant exposure and the hypothalamic programming of metabolism.

Gut-Brain Communication in Parkinson's Disease: Enteroendocrine Regulation by GLP-1.

PURPOSE OF REVIEW: Defective gut-brain communication has recently been proposed as a promoter of neurodegeneration, but mechanisms mediating communication remain elusive. In particular, the Parkinson's disease (PD) phenotype has been associated with both dysbiosis of intestinal microbiota and neuroinflammation. Here, we review recent advances in the PD field that connect these two concepts, providing an explanation based on enteroendocrine signaling from the gut to the brain. RECENT FINDINGS: There have been several recent accounts highlighting the importance of the microbiota-gut-brain axis in PD. The objective of this review is to discuss the role of the neuroendocrine system in gut-brain communication as it relates to PD pathogenesis, as this system has not been comprehensively considered in prior reviews. The incretin hormone glucagon-like peptide 1 (GLP-1) is secreted by enteroendocrine cells of the intestinal epithelium, and there is evidence that it is neuroprotective in animal models and human subjects with PD. Agonists of GLP-1 receptors used in diabetes appear to be useful for preventing neurodegeneration. New tools and models have enabled us to study regulation of GLP-1 secretion by intestinal microbiota, to understand how this process may be defective in PD, and to develop methods for therapeutically modifying disease development or progression using the enteroendocrine system. GLP-1 secretion by enteroendocrine cells may be a key mediator of neuroprotection in PD, and new findings in this field may offer unique insights into PD pathogenesis and therapeutic strategies.

Cell Networks in Endocrine/Neuroendocrine Gland Function.

Reproduction, growth, stress, and metabolism are determined by endocrine/neuroendocrine systems that regulate circulating hormone concentrations. All these systems generate rhythms and changes in hormone pulsatility observed in a variety of pathophysiological states. Thus, the output of endocrine/neuroendocrine systems must be regulated within a narrow window of effective hormone concentrations but must also maintain a capacity for plasticity to respond to changing physiological demands. Remarkably most endocrinologists still have a "textbook" view of endocrine gland organization which has emanated from 20th century histological studies on thin 2D tissue sections. However, 21st -century technological advances, including in-depth 3D imaging of specific cell types have vastly changed our knowledge. We now know that various levels of multicellular organization can be found across different glands, that organizational motifs can vary between species and can be modified to enhance or decrease hormonal release. This article focuses on how the organization of cells regulates hormone output using three endocrine/neuroendocrine glands that present different levels of organization and complexity: the adrenal medulla, with a single neuroendocrine cell type; the anterior pituitary, with multiple intermingled cell types; and the pancreas with multiple intermingled cell types organized into distinct functional units. We give an overview of recent methodologies that allow the study of the different components within endocrine systems, particularly their temporal and spatial relationships. We believe the emerging findings about network organization, and its impact on hormone secretion, are crucial to understanding how homeostatic regulation of endocrine axes is carried out within endocrine organs themselves. © 2022 American Physiological Society. Compr Physiol 12:3371-3415, 2022.

Neuroendocrine-immune Interface: Interactions of Two Complex Systems in Health and Disease.

The relationship between the neuroendocrine and the immune systems is essential to maintain homeostasis. Their complex interactions are present in many physiological or pathological states whereby hormones exert different actions in immune system cells and vice versa. Hormones such as prolactin, growth hormone, cortisol and sex hormones are known to regulate the differentiation and function of immune system cells and the production of cytokines. Many of these cells express hormone receptors leading to the tempering of several autoimmune and neoplastic diseases. The pituitary gland is susceptible to autoimmune damage, be it because of primary lymphocytic hypophysitis, as part of IgG4-related disease or as an adverse event of treatment with immune checkpoint inhibitors (ICi). Finally, pituitary adenomas, like many other neoplasms, are frequently infiltrated by different cells of the immune system, a phenomenon that can be related to the degree of invasiveness of these lesions. The purpose of the present work is to critically analyze the neuroendocrine-immune interphase, from both a biological and a clinical perspective.

Influence of early life stress on depression: from the perspective of neuroendocrine to the participation of gut microbiota.

Depression is the most common mental disorder and has become a heavy burden in modern society. Clinical studies have identified early life stress as one of the high-risk factors for increased susceptibility to depression. Alteration of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress is one of the key risk factors for depression susceptibility related to early life stress. Laboratory animal studies have demonstrated that maternal separation (MS) for extended periods elicits HPA axis changes. These changes persist into adulthood and resemble those present in depressed adult individuals, including hyperactivity of the HPA axis. In addition, there is growing evidence that inflammation plays an important role in depression susceptibility concerned with early life stress. Individuals that have experienced MS have higher levels of pro-inflammatory cytokines and are susceptible to depression. Recently, it has been found that the gut microbiota plays an important role in regulating behavior and is also associated with depression. The translocation of gut microbiota and the change of gut microbiota composition caused by early stress may be a reason. In this review, we discussed the mechanisms by which early life stress contributes to the development of depression in terms of these factors. These studies have facilitated a systematic understanding of the pathogenesis of depression related to early life stress and will provide new ideas for the prevention and treatment of depression.

Advances in Reproductive Endocrinology and Neuroendocrine Research Using Catfish Models.

Catfishes, belonging to the order siluriformes, represent one of the largest groups of freshwater fishes with more than 4000 species and almost 12% of teleostean population. Due to their worldwide distribution and diversity, catfishes are interesting models for ecologists and evolutionary biologists. Incidentally, catfish emerged as an excellent animal model for aquaculture research because of economic importance, availability, disease resistance, adaptability to artificial spawning, handling, culture, high fecundity, hatchability, hypoxia tolerance and their ability to acclimate to laboratory conditions. Reproductive system in catfish is orchestrated by complex network of nervous, endocrine system and environmental factors during gonadal growth as well as recrudescence. Lot of new information on the molecular mechanism of gonadal development have been obtained over several decades which are evident from significant number of scientific publications pertaining to reproductive biology and neuroendocrine research in catfish. This review aims to synthesize key findings and compile highly relevant aspects on how catfish can offer insight into fundamental mechanisms of all the areas of reproduction and its neuroendocrine regulation, from gametogenesis to spawning including seasonal reproductive cycle. In addition, the state-of-knowledge surrounding gonadal development and neuroendocrine control of gonadal sex differentiation in catfish are comprehensively summarized in comparison with other fish models.

The Role of Insulin-like Growth Factor-1 (IGF-1) in the Control of Neuroendocrine Regulation of Growth.

In mammals, the neuroendocrine system, which includes the communication between the hypothalamus and the pituitary, plays a major role in controlling body growth and cellular metabolism. GH produced from the pituitary somatotroph is considered the master regulator of somatic development and involved, directly and indirectly, in carbohydrate and lipid metabolism via complex, yet well-defined, signaling pathways. GH production from the pituitary gland is primarily regulated by the counter-regulatory effects of the hypothalamic GHRH and SST hormones. The role of IGF-1 feedback regulation in GH production has been demonstrated by pharmacologic interventions and in genetically modified mouse models. In the present review, we discuss the role of IGF-1 in the regulation of the GH-axis as it controls somatic growth and metabolic homeostasis. We present genetically modified mouse models that maintain the integrity of the GH/GHRH-axis with the single exception of IGF-1 receptor (IGF-1R) deficiency in the hypothalamic GHRH neurons and somatotroph that reveals a novel mechanism controlling adipose tissues physiology and energy expenditure.

The Role of the Hippocampus in the Neuroendocrine Response to Neurobiological Stimuli in Experiment.

We compared the levels of functional activity of cells in each adrenal zone with blood levels of corticosterone, testosterone, and neuropeptide Y in control and hippocampectomized F1(C57BL/6×DBA/2) mice during modeling of metabolic, motivational, and cognitive tension. The morphofunctional state of the adrenal glands was studied using a new morphometric approach. It was found that hippocampectomy changed the testosterone response to neurobiological stimuli; similar changes were observed in the zona reticularis of the adrenal cortex producing dehydroepiandrosterone that is involved in the regulation of testosterone secretion. At the same time, hippocampectomy enhanced the response of the peptide hormone; the index of functional activity of chromaffin cells producing this hormone also increased. These findings allow us to put forward a hypothesis that the hippocampus is involved in the regulation of mutual influences of the studied hormones and that it modulates the sensitivity of testosterone and NPY to metabolic and cognitive factors.

Fluid Secretion by Malpighian Tubules of Rhodnius prolixus: Neuroendocrine Control With New Insights From a Transcriptome Analysis.

Rhodnius prolixus (the kissing bug and a major vector of Chagas disease) is an obligate blood feeder that in the case of the fifth instar consumes up to 10 times its unfed body weight in a single 20-minute feed. A post-prandial diuresis is initiated, within minutes of the start of gorging, in order to lower the mass and concentrate the nutrients of the meal. Thus, R. prolixus rapidly excretes a fluid that is high in NaCl content and hypo-osmotic to the hemolymph, thereby eliminating 50% of the volume of the blood meal within 3 hours of gorging. In R. prolixus, as with other insects, the Malpighian tubules play a critical role in diuresis. Malpighian tubules are not innervated, and their fine control comes under the influence of the neuroendocrine system that releases amines and neuropeptides as diuretic or antidiuretic hormones. These hormones act upon the Malpighian tubules via a variety of G protein-coupled receptors linked to second messenger systems that influence ion transporters and aquaporins; thereby regulating fluid secretion. Much has been discovered about the control of diuresis in R. prolixus, and other model insects, using classical endocrinological studies. The post-genomic era, however, has brought new insights, identifying novel diuretic and antidiuretic hormone-signaling pathways whilst also validating many of the classical discoveries. This paper will focus on recent discoveries into the neuroendocrine control of the rapid post-prandial diuresis in R. prolixus, in order to emphasize new insights from a transcriptome analysis of Malpighian tubules taken from unfed and fed bugs.