Recent Advances in Endocrine and Neuroendocrine Systems.

The endocrine and neuroendocrine systems exert powerful and broad control over the regulation of homeostasis in animals. Secreted hormones play significant roles in lifetime-related events such as germ cell development, sexual maturation, development, metamorphosis, aging, feeding, and energy metabolism. Additionally, hormones, particularly sex steroid hormones, are involved in reproduction, including sexual behavior and dimorphism. Changes in body color protect against external enemies, and circadian rhythms direct physiology and behaviors in synchrony with light and dark cycles. Water and electrolyte metabolism are essential for survival in land or seawater. Both aquatic and terrestrial animals have developed a variety of endocrine and neuroendocrine systems that exquisitely manage water and electrolyte metabolism to support survival. In zoological science, many animal species are investigated for their unique life history phenomena, and many researchers bring original and unique research approaches to understand these phenomena. Exploring such a variety of animal species leads to an understanding of diversity and unity, and contributes to the development of comparative endocrinology. This Special Issue contains 15 papers focusing on the endocrine mechanisms involved in the aforementioned life phenomena.

Cutaneous-immuno-neuro-endocrine (CINE) system: A complex enterprise transforming skin into a super organ.

Skin is now emerging as a complex realm of three chief systems viz. immune system, nervous system, and endocrine system. The cells involved in their intricate crosstalk, namely native skin cells, intra-cutaneous immune cells and cutaneous sensory neurons have diverse origin and distinct functions. However, recent studies have explored their role beyond their pre-defined functional boundaries, such that the cells shun their traditional functions and adopt unconventional roles. For example, the native skin cells, apart from providing for basic structural framework of skin, also perform special immune functions and participate in extensive neuro-endocrine circuitry, which were traditionally designated as functions of cutaneous resident immune cells and sensory neurons respectively. At the cellular level, this unique collaboration is brought out by special molecules called neuromediators including neurotransmitters, neuropeptides, neurotrophins, neurohormones and cytokines/chemokines. While this intricate crosstalk is essential for maintaining cutaneous homeostasis, its disruption is seen in various cutaneous diseases. Recent study models have led to a paradigm shift in our understanding of pathophysiology of many such disorders. In this review, we have described in detail the interaction of immune cells with neurons and native skin cells, role of neuromediators, the endocrine aspect in skin and current understanding of cutaneous neuro-immuno-endocrine loop in one of the commonest skin diseases, psoriasis. An accurate knowledge of this unique crosstalk can prove crucial in understanding the pathophysiology of different skin diseases and allow for generation of targeted therapeutic modalities.

Photo-neuro-immuno-endocrinology: How the ultraviolet radiation regulates the body, brain, and immune system.

Ultraviolet radiation (UVR) is primarily recognized for its detrimental effects such as cancerogenesis, skin aging, eye damage, and autoimmune disorders. With exception of ultraviolet B (UVB) requirement in the production of vitamin D3, the positive role of UVR in modulation of homeostasis is underappreciated. Skin exposure to UVR triggers local responses secondary to the induction of chemical, hormonal, immune, and neural signals that are defined by the chromophores and extent of UVR penetration into skin compartments. These responses are not random and are coordinated by the cutaneous neuro-immuno-endocrine system, which counteracts the action of external stressors and accommodates local homeostasis to the changing environment. The UVR induces electrical, chemical, and biological signals to be sent to the brain, endocrine and immune systems, as well as other central organs, which in concert regulate body homeostasis. To achieve its central homeostatic goal, the UVR-induced signals are precisely computed locally with transmission through nerves or humoral signals release into the circulation to activate and/or modulate coordinating central centers or organs. Such modulatory effects will be dependent on UVA and UVB wavelengths. This leads to immunosuppression, the activation of brain and endocrine coordinating centers, and the modification of different organ functions. Therefore, it is imperative to understand the underlying mechanisms of UVR electromagnetic energy penetration deep into the body, with its impact on the brain and internal organs. Photo-neuro-immuno-endocrinology can offer novel therapeutic approaches in addiction and mood disorders; autoimmune, neurodegenerative, and chronic pain-generating disorders; or pathologies involving endocrine, cardiovascular, gastrointestinal, or reproductive systems.

α1 and ß3 adrenergic receptor-mediated excitatory effects of adrenaline on the caudal neurosecretory system (CNSS) in olive flounder, Paralichthys olivaceus.

Adrenaline is one of the most important neurotransmitters in the central nervous system and is produced during stress. In this study, we investigated the modulatory role of adrenaline and adrenergic receptors on the neuroendocrine Dahlgren cells in the caudal neurosecretory system (CNSS) of olive flounder. Ex vivo electrophysiological recordings revealed that adrenaline significantly increased the firing frequency and altered the firing pattern of Dahlgren cells. Moreover, treatment with adrenaline led to a significant upregulation of ion channels and major hormone secretion genes in CNSS at the mRNA levels. Additionally, treatment with adrenaline resulted in a significantly elevation in the expression levels of α1- and ß3-adrenergic receptors. Furthermore, the ß3-adrenergic receptor antagonist exerts a significant inhibitory effect on adrenaline-induced enhancement firing activities of Dahlgren cells, whereas the α1-adrenergic receptor antagonist displays a comparatively weaker inhibitory effect. Additionally, the enhanced firing activity induced by adrenaline could be effectively suppressed by both α1- and ß3-adrenergic receptor antagonists. Taken together, these findings provide strong evidence in favor of the excitatory effects of adrenaline through α1 and ß3 adrenergic receptors in CNSS to stimulate the secretion of stress-related hormones, ß3-adrenergic receptor plays a more dominant role in the modulation of firing activities of Dahlgren cells by adrenaline and thereby regulates the stress response in olive flounder.

The evolving concept of multimorbidity and migraine.

Migraine presents with high prevalence and similar clinical course with different disorders such as neurological, psychiatric, cardio- and cerebrovascular, gastrointestinal, metabolic-endocrine, and immunological conditions, which can often cooccur themselves. Multifaceted mechanisms subtend these comorbidities with a bidirectional link. First, a shared genetic load can explain the cooccurrence. Second, comorbid pathologies can promote disproportionate energetic needs, thalamocortical network dysexcitability, and systemic transient or persistent proinflammatory state, which may trigger the activation of a broad self-protective network that includes the trigeminovascular system in conjunction with the neuroendocrine hypothalamic system. This response results in maintenance of brain homeostasis by modulating subcortical-cortical excitability, energetic balance, osmoregulation, and emotional response. In this process, the CGRP is released in the trigeminovascular system. However, the calcitonin gene-related peptide (CGRP) plays several actions also outside the brain to maintain the homeostatic needs and is involved in the physiological functions of different systems, whose disorders are associated with migraine. This aspect further increases the complexity of migraine treatment, where standard therapies often have systemic adverse effects. On the other hand, some preventives can improve comorbid conditions. In summary, we propose that migraine management should involve a multidisciplinary approach to identify and mitigate potential risk factors and comorbidity and tailor therapies individually.

Effects of sociocultural stressors on maternal responsivity and the infant behavioral and neuroendocrine response to stress in families of Mexican descent.

Maternal stress is consistently linked to alterations in maternal behavior and infant neurodevelopmental outcomes. As the Latino population grows in the U.S., it is increasingly important to understand how culturally relevant factors affect this relationship. This study aimed to address the role of sociocultural stressors on maternal sensitivity and markers of infant emotional regulation and the neuroendocrine response to stress in mother/infant dyads of Mexican descent. Pregnant women of Mexican descent (n = 115) were recruited during early pregnancy and followed until their infants were 6 months old. Mothers completed measures of sociocultural stressors (acculturative stress and discrimination) at pre and postnatal time points. At 6 months, dyads underwent the Still Face procedure. Mothers were observed for behaviors exhibiting maternal responsivity, while negative vocalizations were observed in infants. Salivary cortisol was also collected from infants. Maternal responsivity was a salient risk factor for alterations in infant emotional regulation and cortisol activity. Postnatal experiences of discrimination were also negatively associated with infant negative affect. This work highlights maternal responsivity and points to a potential role for experiences of discrimination in the response to stress in the mother/child dyad that may have consequences for the development of emotional regulation in infants of Mexican descent.

The Caenorhabditis elegans neuroendocrine system and their modulators: An overview.

In this review we seek to systematically bring what has been published in the literature about the nervous system, endocrine system, neuroendocrine relationships, neuroendocrine modulations and endocrine disruptors in the alternative model Caenorhabditis elegans. The serotonergic, dopaminergic, GABAergic and glutamatergic neurotransmitters are related to the modulation of the neuroendocrine axis, leading to the activation or inhibition of several processes that occur in the worm through distinct and interconnected pathways. Furthermore, this review addresses the gut-neuronal axis as it has been revealed in recent years that gut microbiota impacts on neuronal functions. This review also approaches xenobiotics that can positively or negatively impact the neuroendocrine system in C. elegans as in mammals, which allows the application of this nematode to screen new drugs and to identify toxicants that are endocrine disruptors.

Evolutionary conserved peptide and glycoprotein hormone-like neuroendocrine systems in C. elegans.

Peptides and protein hormones form the largest group of secreted signals that mediate intercellular communication and are central regulators of physiology and behavior in all animals. Phylogenetic analyses and biochemical identifications of peptide-receptor systems reveal a broad evolutionary conservation of these signaling systems at the molecular level. Substantial progress has been made in recent years on characterizing the physiological and putative ancestral roles of many peptide systems through comparative studies in invertebrate models. Several peptides and protein hormones are not only molecularly conserved but also have conserved roles across animal phyla. Here, we focus on functional insights gained in the nematode Caenorhabditis elegans that, with its compact and well-described nervous system, provides a powerful model to dissect neuroendocrine signaling networks involved in the control of physiology and behavior. We summarize recent discoveries on the evolutionary conservation and knowledge on the functions of peptide and protein hormone systems in C. elegans.

Bisphenol A Analogues Induce Neuroendocrine Disruption via Gut-Brain Regulation in Zebrafish.

There is epidemiological evidence in humans that exposure to endocrine-disrupting chemicals such as bisphenol A (BPA) is tied to abnormal neuroendocrine function with both behavioral and intestinal symptoms. However, the underlying mechanism of this effect, particularly the role of gut-brain regulation, is poorly understood. We exposed zebrafish embryos to a concentration series (including environmentally relevant levels) of BPA and its analogues. The analogue bisphenol G (BPG) yielded the strongest behavioral impact on zebrafish larvae and inhibited the largest number of neurotransmitters, with an effective concentration of 0.5 µg/L, followed by bisphenol AF (BPAF) and BPA. In neurod1:EGFP transgenic zebrafish, BPG and BPAF inhibited the distribution of enteroendocrine cells (EECs), which is associated with decreased neurotransmitters level and behavioral activity. Immune staining of ace-α-tubulin suggested that BPAF inhibited vagal neural development at 50 and 500 µg/L. Single-cell RNA-Seq demonstrated that BPG disrupted the neuroendocrine system by inducing inflammatory responses in intestinal epithelial cells via TNFα-trypsin-EEC signaling. BPAF exposure activated apoptosis and inhibited neural developmental pathways in vagal neurons, consistent with immunofluorescence imaging studies. These findings show that both BPG and BPAF affect the neuroendocrine system through the gut-brain axis but by different mechanisms, revealing new insights into the modes of bisphenol-mediated neuroendocrine disruption.

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.

Crosstalk Between the Neuroendocrine System and Bone Homeostasis.

The homeostasis of bone microenvironment is the foundation of bone health and comprises 2 concerted events: bone formation by osteoblasts and bone resorption by osteoclasts. In the early 21st century, leptin, an adipocytes-derived hormone, was found to affect bone homeostasis through hypothalamic relay and the sympathetic nervous system, involving neurotransmitters like serotonin and norepinephrine. This discovery has provided a new perspective regarding the synergistic effects of endocrine and nervous systems on skeletal homeostasis. Since then, more studies have been conducted, gradually uncovering the complex neuroendocrine regulation underlying bone homeostasis. Intriguingly, bone is also considered as an endocrine organ that can produce regulatory factors that in turn exert effects on neuroendocrine activities. After decades of exploration into bone regulation mechanisms, separate bioactive factors have been extensively investigated, whereas few studies have systematically shown a global view of bone homeostasis regulation. Therefore, we summarized the previously studied regulatory patterns from the nervous system and endocrine system to bone. This review will provide readers with a panoramic view of the intimate relationship between the neuroendocrine system and bone, compensating for the current understanding of the regulation patterns of bone homeostasis, and probably developing new therapeutic strategies for its related disorders.

A bird's eye view of the hippocampus beyond space: Behavioral, neuroanatomical, and neuroendocrine perspectives.

Although the hippocampus is one of the most-studied brain regions in mammals, research on the avian hippocampus has been more limited in scope. It is generally agreed that the hippocampus is an ancient feature of the amniote brain, and therefore homologous between the two lineages. Because birds and mammals are evolutionarily not very closely related, any shared anatomy is likely to be crucial for shared functions of their hippocampi. These functions, in turn, are likely to be essential if they have been conserved for over 300 million years. Therefore, research on the avian hippocampus can help us understand how this brain region evolved and how it has changed over evolutionary time. Further, there is a strong research foundation in birds on hippocampal-supported behaviors such as spatial navigation, food caching, and brood parasitism that scientists can build upon to better understand how hippocampal anatomy, network circuitry, endocrinology, and physiology can help control these behaviors. In this review, we summarize our current understanding of the avian hippocampus in spatial cognition as well as in regulating anxiety, approach-avoidance behavior, and stress responses. Although there are still some questions about the exact number of subdivisions in the avian hippocampus and how that might vary in different avian families, there is intriguing evidence that the avian hippocampus might have complementary functional profiles along the rostral-caudal axis similar to the dorsal-ventral axis of the rodent hippocampus, where the rostral/dorsal hippocampus is more involved in cognitive processes like spatial learning and the caudal/ventral hippocampus regulates emotional states, anxiety, and the stress response. Future research should focus on elucidating the cellular and molecular mechanisms - including endocrinological - in the avian hippocampus that underlie behaviors such as spatial navigation, spatial memory, and anxiety-related behaviors, and in so doing, resolve outstanding questions about avian hippocampal function and organization.

The effect of neuroendocrine abnormalities on the risk of psychiatric readmission after hospitalization for bipolar disorder: A retrospective study.

BACKGROUND: The correlation between the endocrine system and bipolar disorder(BD) has been well recognized, yet the influence of neuroendocrine hormones on readmission risk post-hospitalization for BD remains largely unexplored. This retrospective cohort study was to scrutinize the impact of neuroendocrine functionality on the readmission of patients with BD post-hospitalization for mental disorders. METHODS: The dataset was derived from the electronic medical records of the First Affiliated Hospital of Jinan University in Guangzhou, China. Both univariate and multivariate logistic regression analysis were conducted on all patients hospitalized for BD, and from 1 January 2017 to October 2022. RESULTS: Of the 1110 eligible patients, 83 and 141 patients experienced psychiatric readmissions within 90 and 180 days post-discharge, respectively. Multivariate analysis revealed that high serum TSH levels (aOR = 1.079; 95%CI = 1.003-1.160) and thyroid disease comorbidities (aOR = 2.899; 95%CI = 1.303-6.452) were independently correlated with the risk of 90-day readmission; while increased serum TSH levels (aOR = 1.179; 95%CI = 1.081-1.287) represented a risk factor for 180-day readmission. These results indicate that high serum TSH levels and thyroid disease comorbidities may contribute to an elevated readmission risk in patients with BD following hospitalization. CONCLUSION: Routinely evaluating and intervening in thyroid function is crucial in the treatment of BD, as it may aid in preventing re-hospitalization.

Environmental toxicology of bisphenol A: Mechanistic insights and clinical implications on the neuroendocrine system.

Bisphenol A (BPA) is a widely used environmental estrogen found in a variety of products, including food packaging, canned goods, baby bottle soothers, reusable cups, medical devices, tableware, dental sealants, and other consumer goods. This substance has been found to have detrimental effects on both the environment and human health, particularly on the reproductive, immune, embryonic development, nervous, endocrine, and respiratory systems. This paper aims to provide a comprehensive review of the effects of BPA on the neuroendocrine system, with a primary focus on its impact on the brain, neurons, oligodendrocytes, neural stem cell proliferation, DNA damage, and behavioral development. Additionally, the review explores the clinical implications of BPA, specifically examining its role in the onset and progression of various diseases associated with the neuroendocrine metabolic system. By delving into the mechanistic analysis and clinical implications, this review aims to serve as a valuable resource for studying the impacts of BPA exposure on organisms.

The neuroendocrine system of Ciona intestinalis Type A, a deuterostome invertebrate and the closest relative of vertebrates.

Deuterostome invertebrates, including echinoderms, hemichordates, cephalochordates, and urochordates, exhibit common and species-specific morphological, developmental, physiological, and behavioral characteristics that are regulated by neuroendocrine and nervous systems. Over the past 15 years, omics, genetic, and/or physiological studies on deuterostome invertebrates have identified low-molecular-weight transmitters, neuropeptides and their cognate receptors, and have clarified their various biological functions. In particular, there has been increasing interest on the neuroendocrine and nervous systems of Ciona intestinalis Type A, which belongs to the subphylum Urochordata and occupies the critical phylogenetic position as the closest relative of vertebrates. During the developmental stage, gamma-aminobutylic acid, D-serine, and gonadotropin-releasing hormones regulate metamorphosis of Ciona. In adults, the neuropeptidergic mechanisms underlying ovarian follicle growth, oocyte maturation, and ovulation have been elucidated. This review article provides the most recent and fundamental knowledge of the neuroendocrine and nervous systems of Ciona, and their evolutionary aspects.

Role of stress in skin diseases: A neuroendocrine-immune interaction view.

Psychological stress is a crucial factor in the development of many skin diseases, and the stigma caused by skin disorders may further increase the psychological burden, forming a vicious cycle of psychological stress leading to skin diseases. Therefore, understanding the relationship between stress and skin diseases is necessary. The skin, as the vital interface with the external environment, possesses its own complex immune system, and the neuroendocrine system plays a central role in the stress response of the body. Stress-induced alterations in the immune system can also disrupt the delicate balance of immune cells and inflammatory mediators in the skin, leading to immune dysregulation and increased susceptibility to various skin diseases. Stress can also affect the skin barrier function, impair wound healing, and promote the release of pro-inflammatory cytokines, thereby exacerbating existing skin diseases such as psoriasis, atopic dermatitis, acne, and urticaria. In the present review, we explored the intricate relationship between stress and skin diseases from a neuroendocrine-immune interaction perspective. We explored the occurrence and development of skin diseases in the context of stress, the stress models for skin diseases, the impact of stress on skin function and diseases, and relevant epidemiological studies and clinical trials. Understanding the relationship between stress and skin diseases from a neuroendocrine-immune interaction perspective provides a comprehensive framework for targeted interventions and new insights into the diagnosis and treatment of skin diseases.

Imprinting and Reproductive Health: A Toxicological Perspective.

This overview discusses the role of imprinting in the development of an organism, and how exposure to environmental chemicals during fetal development leads to the physiological and biochemical changes that can have adverse lifelong effects on the health of the offspring. There has been a recent upsurge in the use of chemical products in everyday life. These chemicals include industrial byproducts, pesticides, dietary supplements, and pharmaceutical products. They mimic the natural estrogens and bind to estradiol receptors. Consequently, they reduce the number of receptors available for ligand binding. This leads to a faulty signaling in the neuroendocrine system during the critical developmental process of 'imprinting'. Imprinting causes structural and organizational differentiation in male and female reproductive organs, sexual behavior, bone mineral density, and the metabolism of exogenous and endogenous chemical substances. Several studies conducted on animal models and epidemiological studies provide profound evidence that altered imprinting causes various developmental and reproductive abnormalities and other diseases in humans. Altered metabolism can be measured by various endpoints such as the profile of cytochrome P-450 enzymes (CYP450's), xenobiotic metabolite levels, and DNA adducts. The importance of imprinting in the potentiation or attenuation of toxic chemicals is discussed.