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Ecdysteroid molting hormones coordinate arthropod growth and development. Binding of 20-hydroxyecdysone (20E) to ecdysteroid receptor EcR/RXR activates a cascade of nuclear receptor transcription factors that mediate tissue responses to hormone. Insect ecdysteroid responsive and Forkhead box class O (FOXO) transcription factor gene sequences were used to extract orthologs from blackback land crab (Gecarcinus lateralis) Y-organ (YO) transcriptome: Gl-Ecdysone Receptor (EcR), Gl-Broad Complex (Br-C), Gl-E74, Gl-Hormone Receptor 3 (HR3), Gl-Hormone Receptor 4 (HR4), Gl-FOXO, and Gl-Fushi tarazu factor-1 (Ftz-f1). Quantitative polymerase chain reaction quantified mRNA levels in tissues from intermolt animals and in YO of animals induced to molt by multiple limb autotomy (MLA) or eyestalk ablation (ESA). Gl-EcR, Gl-Retinoid X Receptor (RXR), Gl-Br-C, Gl-HR3, Gl-HR4, Gl-E74, Gl-E75, Gl-Ftz-f1, and Gl-FOXO were expressed in all 10 tissues, with Gl-Br-C, Gl-E74, Gl-E75, and Gl-HR4 mRNA levels in the YO lower than those in most of the other tissues. In MLA animals, molting had no effect on Gl-Br-C, Gl-E74, and Gl-Ftz-f1 mRNA levels and little effect on Gl-EcR, Gl-E75, and Gl-HR4 mRNA levels. Gl-HR3 and Gl-FOXO mRNA levels were increased during premolt stages, while Gl-RXR mRNA level was highest during intermolt and premolt stages and lowest at postmolt stage. In ESA animals, YO mRNA levels were not correlated with hemolymph ecdysteroid titers. ESA had no effect on Gl-EcR, Gl-E74, Gl-HR3, Gl-HR4, Gl-Ftz-f1, and Gl-FOXO mRNA levels, while Gl-RXR, Gl-Br-C, and Gl-E75 mRNA levels were decreased at 3 days post-ESA. These data suggest that transcriptional up-regulation of Gl-FOXO and Gl-HR3 contributes to increased YO ecdysteroidogenesis during premolt. By contrast, transcriptional regulation of ecdysteroid responsive genes and ecdysteroidogenesis were uncoupled in the YO of ESA animals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mutations in LRBA, a BEACH domain protein, cause severe immune deficiency in humans. LRBA is expressed in many tissues and organs according to biochemical analysis, but little is known about its cellular and subcellular localization, and its deficiency phenotype outside the immune system. By LacZ histochemistry of Lrba gene-trap mice, we performed a comprehensive survey of LRBA expression in numerous tissues, detecting it in many if not all epithelia, in exocrine and endocrine cells, and in subpopulations of neurons. Immunofluorescence microscopy of the exocrine and endocrine pancreas, salivary glands, and intestinal segments, confirmed these patterns of cellular expression and provided information on the subcellular localizations of the LRBA protein. Immuno-electron microscopy demonstrated that in neurons and endocrine cells, which co-express LRBA and its closest relative, neurobeachin, both proteins display partial association with endomembranes in complementary, rather than overlapping, subcellular distributions. Prominent manifestations of human LRBA deficiency, such as inflammatory bowel disease or endocrinopathies, are believed to be primarily due to immune dysregulation. However, as essentially all affected tissues also express LRBA, it is possible that LRBA deficiency enhances their vulnerability and contributes to the pathogenesis., (© 2024. The Author(s).)

The natriuretic peptide family consists of three biologically active peptides: atrial natriuretic peptide (ANP), brain (or B-type) natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). ANP and BNP, secreted by the heart, act as cardiac hormones, whereas CNP is an endothelial peptide. The aim of this manuscript is to review the production, action mechanisms, effects and clinical applications of natriuretic peptides., (Copyright © 2021. Published by Elsevier Masson SAS.)

Imprinting control region (ICR1) controls the expression of the Igf2 and H19 genes in a parent-of-origin specific manner. Appropriate expression of the Igf2-H19 locus is fundamental for normal fetal development, yet the importance of ICR1 in the placental production of hormones that promote maternal nutrient allocation to the fetus is unknown. To address this, we used a novel mouse model to selectively delete ICR1 in the endocrine junctional zone (Jz) of the mouse placenta (Jz-ΔICR1). The Jz-ΔICR1 mice exhibit increased Igf2 and decreased H19 expression specifically in the Jz. This was accompanied by an expansion of Jz endocrine cell types due to enhanced rates of proliferation and increased expression of pregnancy-specific glycoprotein 23 in the placenta of both fetal sexes. However, changes in the endocrine phenotype of the placenta were related to sexually-dimorphic alterations to the abundance of Igf2 receptors and downstream signalling pathways (Pi3k-Akt and Mapk). There was no effect of Jz-ΔICR1 on the expression of targets of the H19-embedded miR-675 or on fetal weight. Our results demonstrate that ICR1 controls placental endocrine capacity via sex-dependent changes in signalling., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

The mammary gland (MG) and female prostate are plastic reproductive organs which are highly responsive to hormones. Thus, endocrine disruptors, such as bisphenol A (BPA) and exogenous estrogens, negatively affect glandular homeostasis. In addition to previously described alterations, changes in inflammatory markers expression also trigger the development of a microenvironment that contributes to tumor progression. The current work aimed to evaluate the inflammatory responses of the MG and prostate gland to BPA (50 µg/kg) and 17-β estradiol (35 µg/kg) exposure during the perinatal window of susceptibility. The results showed that at 6 months of age there was an increase in the number of phospho-STAT3 (P-STAT3) positive cells in the female prostate from animals perinatally exposed to 50 µg/kg BPA daily. In addition, the number of macrophages increased in these animals in comparison with nonexposed animals, as shown by the F4/80 marker. Despite an increase in the incidence of lobuloalveolar and intraductal hyperplasia, the MG did not show any difference in the expression of the four inflammatory markers evaluated: tumor necrosis factor-α, COX-2, P-STAT3, and F4/80. Analysis of both glands from the same animal led to the conclusion that exposure to endocrine disruptors during the perinatal window of susceptibility leads to different inflammatory responses in different reproductive organs. As the prostate is more susceptible to these inflammatory mechanisms, it is reasonable to affirm that possible neoplastic alterations in this organ are related to changes in the inflammatory pattern of the stroma, a characteristic that is not evident in the MG., (© 2021 International Federation for Cell Biology.)

H2A.J is a poorly studied mammalian-specific variant of histone H2A. We used immunohistochemistry to study its localization in various human and mouse tissues. H2A.J showed cell-type specific expression with a striking enrichment in luminal epithelial cells of multiple glands including those of breast, prostate, pancreas, thyroid, stomach, and salivary glands. H2A.J was also highly expressed in many carcinoma cell lines and in particular, those derived from luminal breast and prostate cancer. H2A.J thus appears to be a novel marker for luminal epithelial cancers. Knocking-out the H2AFJ gene in T47D luminal breast cancer cells reduced the expression of several estrogen-responsive genes which may explain its putative tumorigenic role in luminal-B breast cancer.

Fat stores are critical for reproductive success and may govern maturation initiation. Here, we report that signaling and sensing fat sufficiency for sexual maturation commitment requires the lipid carrier apolipophorin in fat cells and Sema1a in the neuroendocrine prothoracic gland (PG). Larvae lacking apolpp or Sema1a fail to initiate maturation despite accruing sufficient fat stores, and they continue gaining weight until death. Mechanistically, sensing peripheral body-fat levels via the apolipophorin/Sema1a axis regulates endocytosis, endoplasmic reticulum remodeling, and ribosomal maturation for the acquisition of the PG cells' high biosynthetic and secretory capacity. Downstream of apolipophorin/Sema1a, leptin-like upd2 triggers the cessation of feeding and initiates sexual maturation. Human Leptin in the insect PG substitutes for upd2, preventing obesity and triggering maturation downstream of Sema1a. These data show how peripheral fat levels regulate the control of the maturation decision-making process via remodeling of endomembranes and ribosomal biogenesis in gland cells., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Coronaviruses are a big family of viruses that can infect mammalians and birds. In humans they mainly cause respiratory tract infections, with a large spectrum of severity, from mild, self-limited infections to highly lethal forms as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and Coronavirus Disease 2019 (COVID-19). Scanty data are reported for the involvement of endocrine glands in human coronaviruses, in particular SARS-CoV-2. In this review, we summarize endocrinological involvement in human coronaviruses, including data on animal coronaviruses. Avians, ferrets and bovine are affected by specific coronavirus syndromes, with variable involvement of endocrine glands. SARS-CoV and SARS-CoV-2 use angiotensin-converting enzyme 2 (ACE2) as a target receptor, so ACE2 plays a central role in viral transmission and initial organ involvement. Autoptic studies on SARS patients revealed that thyroid, parathyroid, pituitary gland, endocrine pancreas and especially adrenals and testis could be impaired by different mechanisms (direct damage by SARS-CoV, inflammation, vascular derangement and autoimmune reactions) and few clinical studies have evidenced functional endocrine impairment. Only few data are available for COVID-19 and gonads and endocrine pancreas seem to be involved. International endocrinological societies have brought some recommendations for the COVID-19 pandemic, but further studies need to be performed, especially to detect long-term hormonal sequelae., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Blue crabs (Callinectes sapidus) undergo incremental growth involving the shedding (molting) of the old exoskeleton, and subsequent expansion and re-calcification of the newly synthesized one. The cellular events that lead to molting are triggered by steroid hormones termed ecdysteroids released from Y-organs, paired endocrine glands located in the anterior cephalothorax. The regulatory pathways leading to increased synthesis and release of ecdysteroids are not fully understood, and no transcriptome has yet been published for blue crab Y-organs. Here we report de novo transcriptome assembly and annotation for adult blue crab Y-organs, and differential gene expression (DGE) analysis between Y-organs of intermolt and premolt crabs. After trimming and quality assessment, a total of 91,819,458 reads from four cDNA libraries were assembled using Trinity to form the reference transcriptome. Trinity produced a total of 171,530 contigs coding for 150,388 predicted genes with an average contig length of 613 and an N50 of 940. Of these, TransDecoder predicted 31,661 open reading frames (ORFs), and 10,210 produced non-redundant blastx results through Trinotate annotation. Genes involved in multiple cell signaling pathways, including Ca 2+ signaling, cGMP signaling, cAMP signaling, and mTOR signaling were present in the annotated reference transcriptome. DGE analysis showed in premolt Y-organs up-regulated genes involved in energy production, cholesterol metabolism, and exocytosis. The results provide insights into the transcriptome of blue crab Y-organs during a natural (rather than experimentally induced) molting cycle, and constitute a step forward in understanding the cellular mechanisms that underlie stage-specific changes in the synthesis and secretion of ecdysteroids by Y-organs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This study reports that parathymosin (PTMS) is secreted by hypothalamic stem/progenitor cells (htNSC) to inhibit senescence of recipient cells such as fibroblasts. Upon release, PTMS is rapidly transferred into the nuclei of various cell types, including neuronal GT1-7 cells and different peripheral cells, and it is effectively transferred into neuronal nuclei in various brain regions in vivo. Notably, brain neurons also produce and release PTMS, and because neuronal populations are large, they are important for maintaining PTMS in the cerebrospinal fluid which is further transferable into the blood. Compared with several other brain regions, the hypothalamus is stronger for long-distance PTMS transfer, supporting a key hypothalamic role in this function. In physiology, aging is associated with declines in PTMS production and transfer in the brain, and ptms knockdown in the hypothalamus versus hippocampus were studied showing different contributions to neurobehavioral physiology. In conclusion, the brain is an endocrine organ through secretion and nuclear transfer of PTMS, and the hypothalamus-brain orchestration of this function is protective in physiology and counteractive against aging-related disorders., (© 2020 Yu et al.)

Our objective was to explore the physiological role of the intestinal endocannabinoids in the regulation of appetite upon short-term exposure to high-fat-diet (HFD) and understand the mechanisms responsible for aberrant gut-brain signaling leading to hyperphagia in mice lacking Napepld in the intestinal epithelial cells (IECs). We generated a murine model harboring an inducible NAPE-PLD deletion in IECs ( Napepld ΔIEC ). After an overnight fast, we exposed wild-type (WT) and Napepld ΔIEC mice to different forms of lipid challenge (HFD or gavage), and we compared the modification occurring in the hypothalamus, in the vagus nerve, and at endocrine level 30 and 60 min after the stimulation. Napepld ΔIEC mice displayed lower hypothalamic levels of N -oleoylethanolamine (OEA) in response to HFD. Lower mRNA expression of anorexigenic Pomc occurred in the hypothalamus of Napepld ΔIEC mice after lipid challenge. This early hypothalamic alteration was not the consequence of impaired vagal signaling in Napepld ΔIEC mice. Following lipid administration, WT and Napepld ΔIEC mice had similar portal levels of glucagon-like peptide-1 (GLP-1) and similar rates of GLP-1 inactivation. Administration of exendin-4, a full agonist of GLP-1 receptor (GLP-1R), prevented the hyperphagia of Napepld ΔIEC mice upon HFD. We conclude that in response to lipid, Napepld ΔIEC mice displayed reduced OEA in brain and intestine, suggesting an impairment of the gut-brain axis in this model. We speculated that decreased levels of OEA likely contributes to reduce GLP-1R activation, explaining the observed hyperphagia in this model. Altogether, we elucidated novel physiological mechanisms regarding the gut-brain axis by which intestinal NAPE-PLD regulates appetite rapidly after lipid exposure.

Objective: To characterise the role of VEGF, EG-VEGF and its receptors in the development and progression of HNC., Design: Human serum and tissues samples were collected from healthy, epulis and HNC patients and used for ELISA assays and immunohistochemistry studies, respectively., Setting: Ibn Rochd Hospital of Casablanca (Morocco), INSERM and University of Grenoble Alpes (France)., Participants: We used serum from 64 patients with head and neck cancers and from 71 controls without general pathology. Tissues samples were collected from seven patients with OSCC and from seven patients with Epulis., Main Outcome Measures: We compared circulating VEGF and EG-VEGF in normal and HNC patients and determined the expression, localisation and quantification of VEGF, EG-VEGF and its receptors; PROKR1 and PROKR2 as well as Ki67, CD31 and CD34 in OSCC and Epulis patients., Results: Both EG-VEGF and VEGF circulating levels were significantly decreased in the HNC (P < .01). OSCC patients expressed less EG-VEGF and VEGF proteins, higher PROKR1 and PROKR2 with no change in CD31 and CD34 levels. A significant increase in Ki67 was observed in OSCC., Conclusions: We demonstrated that circulating VEGF and EG-VEGF are downregulated in HNC patients and in OSCC tissue. EG-VEGF receptors were increased in OSCC, along with a stabilisation of two key markers of angiogenesis. These findings strongly suggest that downregulation of angiogenesis in HNC might explain its moderate metastatic feature., (© 2020 John Wiley & Sons Ltd.)

Stress activates a complex network of hormones known as the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis is dysregulated in chronic stress and psychiatric disorders, but the origin of this dysregulation is unclear and cannot be explained by current HPA models. To address this, we developed a mathematical model for the HPA axis that incorporates changes in the total functional mass of the HPA hormone-secreting glands. The mass changes are caused by HPA hormones which act as growth factors for the glands in the axis. We find that the HPA axis shows the property of dynamical compensation, where gland masses adjust over weeks to buffer variation in physiological parameters. These mass changes explain the experimental findings on dysregulation of cortisol and ACTH dynamics in alcoholism, anorexia, and postpartum. Dysregulation occurs for a wide range of parameters and is exacerbated by impaired glucocorticoid receptor (GR) feedback, providing an explanation for the implication of GR in mood disorders. These findings suggest that gland-mass dynamics may play an important role in the pathophysiology of stress-related disorders., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)

Some endocrine organs are frequent targets of autoimmune attack. Here, we addressed the origin of autoimmune disease from the viewpoint of feedback control. Endocrine tissues maintain mass through feedback loops that balance cell proliferation and removal according to hormone-driven regulatory signals. We hypothesized the existence of a dedicated mechanism that detects and removes mutant cells that missense the signal and therefore hyperproliferate and hypersecrete with potential to disrupt organismal homeostasis. In this mechanism, hypersecreting cells are preferentially eliminated by autoreactive T cells at the cost of a fragility to autoimmune disease. The "autoimmune surveillance of hypersecreting mutants" (ASHM) hypothesis predicts the presence of autoreactive T cells in healthy individuals and the nature of self-antigens as peptides from hormone secretion pathway. It explains why some tissues get prevalent autoimmune disease, whereas others do not and instead show prevalent mutant-expansion disease (e.g., hyperparathyroidism). The ASHM hypothesis is testable, and we discuss experimental follow-up., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

In Drosophila , the larval prothoracic gland integrates nutritional status with developmental signals to regulate growth and maturation through the secretion of the steroid hormone ecdysone. While the nutritional signals and cellular pathways that regulate prothoracic gland function are relatively well studied, the transcriptional regulators that orchestrate the activity of this tissue remain less characterized. Here, we show that lysine demethylase 5 (KDM5) is essential for prothoracic gland function. Indeed, restoring kdm5 expression only in the prothoracic gland in an otherwise kdm5 null mutant animal is sufficient to rescue both the larval developmental delay and the pupal lethality caused by loss of KDM5. Our studies show that KDM5 functions by promoting the endoreplication of prothoracic gland cells, a process that increases ploidy and is rate limiting for the expression of ecdysone biosynthetic genes. Molecularly, we show that KDM5 activates the expression of the receptor tyrosine kinase torso , which then promotes polyploidization and growth through activation of the MAPK signaling pathway. Taken together, our studies provide key insights into the biological processes regulated by KDM5 and expand our understanding of the transcriptional regulators that coordinate animal development., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

Iron Regulatory Protein 1 (IRP1) is a bifunctional cytosolic iron sensor. When iron levels are normal, IRP1 harbours an iron-sulphur cluster (holo-IRP1), an enzyme with aconitase activity. When iron levels fall, IRP1 loses the cluster (apo-IRP1) and binds to iron-responsive elements (IREs) in messenger RNAs (mRNAs) encoding proteins involved in cellular iron uptake, distribution, and storage. Here we show that mutations in the Drosophila 1,4-Alpha-Glucan Branching Enzyme (AGBE) gene cause porphyria. AGBE was hitherto only linked to glycogen metabolism and a fatal human disorder known as glycogen storage disease type IV. AGBE binds specifically to holo-IRP1 and to mitoNEET, a protein capable of repairing IRP1 iron-sulphur clusters. This interaction ensures nuclear translocation of holo-IRP1 and downregulation of iron-dependent processes, demonstrating that holo-IRP1 functions not just as an aconitase, but throttles target gene expression in anticipation of declining iron requirements.

The prolactin receptor (Prlr) mediates not only the multiple effects of prolactin, but also those of the placental lactogens and, in humans, some actions of growth hormone. Although Prlr expression has been reported to be widespread in the body, specific cellular expression patterns within tissues are undefined for many organs. One persisting problem in investigating Prlr function is that the protein is difficult to detect using conventional methods. To allow investigation of Prlr expression with a single cell resolution, we have recently developed a knock-in mouse strain in which Cre recombinase is expressed together with the long isoform of the Prlr using an internal ribosome entry site. When crossed to a Cre-dependent reporter mouse strain, Cre-mediated recombination will genetically label cells that acutely express the Prlr as well as cells that have transiently expressed the Prlr during development. We report here the anatomical distribution of cells which express the fluorescent reporter τ green fluorescent protein in a total of 38 organs prepared from young adult male and female Prlr reporter mice. Our results establish a resource for dissecting the functional role of Prlr in multiple murine tissues., (Copyright © 2019 Endocrine Society.)

The liver is a dynamic organ that plays critical roles in many physiological processes, including the regulation of systemic glucose and lipid metabolism. Dysfunctional hepatic lipid metabolism is a cause of nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disorder worldwide, and is closely associated with insulin resistance and type 2 diabetes. Through the use of advanced mass spectrometry "omics" approaches and detailed experimentation in cells, mice, and humans, we now understand that the liver secretes a wide array of proteins, metabolites, and noncoding RNAs (miRNAs) and that many of these secreted factors exert powerful effects on metabolic processes both in the liver and in peripheral tissues. In this review, we summarize the rapidly evolving field of "hepatokine" biology with a particular focus on delineating previously unappreciated communication between the liver and other tissues in the body. We describe the NAFLD-induced changes in secretion of liver proteins, lipids, other metabolites, and miRNAs, and how these molecules alter metabolism in liver, muscle, adipose tissue, and pancreas to induce insulin resistance. We also synthesize the limited information that indicates that extracellular vesicles, and in particular exosomes, may be an important mechanism for intertissue communication in normal physiology and in promoting metabolic dysregulation in NAFLD., (Copyright © 2019 Endocrine Society.)

The androgenic gland (AG) is a male-specific endocrine organ that controls the primary and secondary sexual characteristics in male crustaceans. More evidence indicates that the insulin-like androgenic gland hormone gene ( IAG ) is the key male sexual differentiation factor, particularly the application of RNA interference (RNAi) technology on IAG . In this study, the full-length cDNA of IAG (termed PcIAG ) was isolated from the red swamp crayfish, Procambarus clarkii . Tissue distribution analysis showed that in addition to its expression in the AG of male P. clarkii , PcIAG was widely expressed in female tissues and other male tissues. The PcIAG protein was detected in the reproductive and nervous systems of adult male P. clarkii . Additionally, RNAi results showed that the PcIAG expression could be silenced efficiently, and the male sperm maturation and release possibly present a transient adverse interference at lower doses (0.1 μg/g and 1 μg/g) of PcIAG-dsRNA ( PcIAG double-stranded RNA). Dramatically, the expression level of PcIAG increased sharply shortly after the injection of higher doses (5 μg/g and 10 μg/g) of PcIAG-dsRNA, which might accelerate the maturation and release of sperm. Moreover, the expression of PcSxl ( P. clarkii Sex-lethal ) was detected by Quantitative Real-Time PCR (qPCR) after the injection of PcIAG-dsRNA to explore whether the PcIAG gene regulates the PcSxl gene, and we found that the PcIAG did not directly regulate PcSxl in P. clarkii . The study could help accelerate the progress of PcIAG functional research and provide a useful reference for the single-sex selective breeding of P. clarkii .

The prothoracic gland (PG) is an important endocrine organ of synthesis and secretion of ecdysteroids that play critical roles in insects. Here, we used a comparative transcriptomic approach to characterize some common features of PGs from two lepidopteran species Bombyx mori and Antheraea pernyi. Functional and pathway annotations revealed an overall similarity in gene profile between the two PG transcriptomes. As expected, almost all steroid hormone biosynthesis genes and the prothoracicitropic hormone receptor gene (Torso) were well represented in the two PGs. Impressively, two ecdysone receptor genes, eleven juvenile hormone related genes, more than 10 chemosensory protein genes, and a set of genes involved in circadian clock were also presented in the two PGs. Quantitative real time -PCR (qRT-PCR) validated the expression of 8 juvenile hormone and 12 clock related genes in B. mori PG, and revealed a different expression pattern during development in whole fifth larval instar. This contribution to insect PG transcriptome data will extend our understanding of the function and regulation of this important organ.

Bacterial lipopolysaccharide (LPS) can contribute to the pathogenesis and the clinical symptoms of many diseases such as cancer, mental disorders, neurodegenerative as well as metabolic diseases. The asymptomatic carrier state of Salmonella spp. is a very important public health problem. A subclinical single dose of LPS obtained from S. Enteritidis (5 μg/kg, i.v.) was administered to discern the consequences of changes of various brain peptides such as corticotropin-releasing hormone (CRH), gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), galanin (GAL), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP), and vasoactive intestinal polypeptide (VIP) in selected clinically important brain sections and endocrine glands of the hypothalamic-pituitary-adrenal (HPA), -thyroid (HPT), -ovarian (HPO) axes. The study was conducted on ten immature crossbred female pigs. The brain peptides were extracted from the hypothalamus (medial basal hypothalamus, preoptic area, lateral hypothalamic area, mammillary bodies, and the stalk median eminence), and pituitary gland (adenohypophysis and neurohypophysis) sections and from the ovaries and adrenal and thyroid glands. There was no difference in health status between LPS and the control groups during the period of the experiment. Nevertheless, even a low single dose of LPS from S. Enteritidis that did not result in any clinical symptoms of disease induced dysregulation of various brain peptides, such as CRH, GnRH, TRH, GAL, NPY, SOM, SP, and VIP in selected brain sections of hypothalamus, pituitary gland and in the endocrine glands of the HPA, HPO, and HPT axes. In conclusion, the obtained results clearly show that subclinical LPS from S. Enteritidis can affect the brain chemistry structure and dysregulate bioactive substance from selected brain sections and glands of the neuroendocrine axes. The exact mechanisms by which LPS can influence major neuroendocrine axes are not fully understood and require further studies.

For over 100 years, there has been an incredible amount of knowledge amassed concerning hormones in the endocrine system and their central role in human health. Hormones represent a diverse group of biomolecules that are released by glands, communicate signals to their target tissue, and are regulated by feedback loops to maintain organism health. Many disease states, such as diabetes and reproductive disorders, stem from misregulation or dysfunction of hormones. Increasing research is illuminating the intricate roles of metal ions in the endocrine system where they may act advantageously in concert with hormones or deleteriously catalyze hormone-associated disease states. As the critical role of metal ions in the endocrine system becomes more apparent, it is increasingly important to untangle the complex mechanisms underlying the connections between inorganic biochemistry and hormone function to understand and control endocrinological phenomena. This tutorial review harmonizes the interdisciplinary fields of endocrinology and inorganic chemistry in the newly-termed field of "metalloendocrinology". We describe examples linking metals to both normal and aberrant hormone function with a focus on highlighting insight to molecular mechanisms. Hormone activities related to both essential metal micronutrients, such as copper, iron, zinc, and calcium, and disruptive nonessential metals, such as lead and cadmium are discussed.

Body mass and body fat composition are of clinical interest due to their links to cardiovascular- and metabolic diseases. Fat stored in the trunk has been suggested to be more pathogenic compared to fat stored in other compartments. In this study, we perform genome-wide association studies (GWAS) for the proportion of body fat distributed to the arms, legs and trunk estimated from segmental bio-electrical impedance analysis (sBIA) for 362,499 individuals from the UK Biobank. 98 independent associations with body fat distribution are identified, 29 that have not previously been associated with anthropometric traits. A high degree of sex-heterogeneity is observed and the effects of 37 associated variants are stronger in females compared to males. Our findings also implicate that body fat distribution in females involves mesenchyme derived tissues and cell types, female endocrine tissues as well as extracellular matrix maintenance and remodeling.

Background and Objective: An overview of the history of endocrinology indicates that definitions of some initially developed concepts, including the term 'hormone' have been changed over time. This review provides a historical overview of current definitions of 'hormone' and the criteria of a true hormone. In addition, a brief history of hormone-related concepts and their transformation over time are discussed., Results: Classically, a hormone is a chemical substance secreted into the bloodstream and acts on distant tissues, usually in a regulatory fashion. Several newly discovered bioregulators and chemical signaling molecules are far from the classical definition of a true hormone and could not fulfill many relevant criteria. Major developments in the field of endocrinology accompanied by the complex terminology, currently used to describe hormonal actions of chemical messengers, underscore the need of the revision of such classical concepts., Conclusion: Complex terminology currently used to describe different hormonal actions of chemical messengers, suggests that it is time to conceptualize the term hormone and revise its classical definition., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Identification of signals for systemic adaption of hormonal regulation would help to understand the crosstalk between cells and environmental cues contributing to growth, metabolic homeostasis and development. Physiological states are controlled by precise pulsatile hormonal release, including endocrine steroids in human and ecdysteroids in insects. We show in Drosophila that regulation of genes that control biosynthesis and signaling of the steroid hormone ecdysone, a central regulator of developmental progress, depends on the extracellular matrix protein Obstructor-A (Obst-A). Ecdysone is produced by the prothoracic gland (PG), where sensory neurons projecting axons from the brain integrate stimuli for endocrine control. By defining the extracellular surface, Obst-A promotes morphogenesis and axonal growth in the PG. This process requires Obst-A-matrix reorganization by Clathrin/Wurst-mediated endocytosis. Our data identifies the extracellular matrix as essential for endocrine ring gland function, which coordinates physiology, axon morphogenesis, and developmental programs. As Obst-A and Wurst homologs are found among all arthropods, we propose that this mechanism is evolutionary conserved., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Peribiliary glands (PBGs) are accessory glands with mucinous and serous acini in the biliary tree. The PBG is composed of a heterogeneous cell population, such as mucus- and pancreatic enzyme-producing epithelial cells, whereas it constitutes niches for multipotential stem/progenitor cells in the human extrahepatic bile duct (EHBD). By contrast, the nature of PBGs in the mouse EHBD remains unclear. Our aim was to establish a method for isolating and characterizing PBG-constituting cells in the mouse EHBD. We found that trophoblast cell surface protein 2 (Trop2) was expressed in the luminal epithelium of mouse EHBD exclusively, but not in the PBG. On the basis of the differential expression profile of Trop2, lumen-forming biliary epithelial cells (LBECs) and PBG-constituting epithelial cells (PBECs) were separately isolated for further characterization. Gene expression analysis revealed that the isolated mouse PBECs expressed several marker genes related to human PBGs. In the colony formation assay, PBECs showed significantly higher colony formation capacity than LBECs. In the organoid formation assay, PBECs formed cystic organoid with LBEC-like phenotype. Interestingly, PBECs proliferated, accompanied by reexpression of Trop2 in vivo after bile duct ligation. Furthermore, the unique expression profile of Trop2 was conserved in human EHBD. Our findings indicate that Trop2 is a useful marker in investigating the pathophysiological roles and characteristics of mouse and human PBGs in biliary diseases., (Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Collectin liver 1 (CL-L1, alias collectin 10) and collectin kidney 1 (CL-K1, alias collectin 11) are oligomeric pattern recognition molecules associated with the complement system, and mutations in either of their genes may lead to deficiency and developmental defects. The two collectins are reportedly localized and synthesized in the liver, kidneys, and adrenals, and can be found in the circulation as heteromeric complexes (CL-LK), which upon binding to microbial high mannose-like glycoconjugates activates the complement system via the lectin activation pathway. The tissue distribution of homo- vs. heteromeric CL-L1 and -K1 complexes, the mechanism of heteromeric complex formation and in which tissues this occurs, is hitherto incompletely described. We have by immunohistochemistry using monoclonal antibodies addressed the precise cellular localization of the two collectins in the main human tissues. We find that the two collectins have widespread and almost identical tissue distribution with a high expression in epithelial cells in endo-/exocrine secretory tissues and mucosa. There is also accordance between localization of mRNA transcripts and detection of proteins, showing that local synthesis likely is responsible for peripheral localization and eventual formation of the CL-LK complexes. The functional implications of the high expression in endo-/exocrine secretory tissue and mucosa is unknown but might be associated with the activity of MASP-3, which has a similar pattern of expression and is known to potentiate the activity of the alternative complement activation pathway.

Background: The prothoracic gland (PG), the principal steroidogenic organ of insects, has been proposed as a model for steroid hormone biosynthesis and regulation., Results: To validate the robustness of the model, we present an analysis of accumulated transcriptomic data from PGs of two model species, Drosophila melanogaster and Bombyx mori. We identify that the common core components of the model in both species are encoded by nine genes. Five of these are Halloween genes whose expression differs substantially between the PGs of these species., Conclusions: We conclude that the PGs can be a model for steroid hormone synthesis and regulation within the context of mitochondrial cholesterol transport and steroid biosynthesis but beyond these core mechanisms, gene expression in insect PGs is too diverse to fit in a context-specific model and should be analysed within a species-specific framework.

Circadian clocks impose daily periodicities to animal behavior and physiology. At their core, circadian rhythms are produced by intracellular transcriptional/translational feedback loops (TTFL). TTFLs may be altered by extracellular signals whose actions are mediated intracellularly by calcium and cAMP. In mammals these messengers act directly on TTFLs via the calcium/cAMP-dependent transcription factor, CREB. In the fruit fly, Drosophila melanogaster, calcium and cAMP also regulate the periodicity of circadian locomotor activity rhythmicity, but whether this is due to direct actions on the TTFLs themselves or are a consequence of changes induced to the complex interrelationship between different classes of central pacemaker neurons is unclear. Here we investigated this question focusing on the peripheral clock housed in the non-neuronal prothoracic gland (PG), which, together with the central pacemaker in the brain, controls the timing of adult emergence. We show that genetic manipulations that increased and decreased the levels of calcium and cAMP in the PG caused, respectively, a shortening and a lengthening of the periodicity of emergence. Importantly, knockdown of CREB in the PG caused an arrhythmic pattern of eclosion. Interestingly, the same manipulations directed at central pacemaker neurons caused arrhythmicity of eclosion and of adult locomotor activity, suggesting a common mechanism. Our results reveal that the calcium and cAMP pathways can alter the functioning of the clock itself. In the PG, these messengers, acting as outputs of the clock or as second messengers for stimuli external to the PG, could also contribute to the circadian gating of adult emergence., Competing Interests: The authors have declared that no competing interests exist.

Significance: Hydrogen sulfide (H 2 S) at the right concentration is associated with numerous health benefits in experimental organisms, ranging from protection from ischemia/reperfusion injury to life span extension. Given the considerable translation potential, two major strategies have emerged: supplementation of exogenous H 2 S and modulation of endogenous H 2 S metabolism. Recent Advances: Recently, it was reported that hepatic H 2 S production capacity is increased in two of the best-characterized mammalian models of life span extension, dietary restriction, and hypopituitary dwarfism, leading to new insights into dietary and hormonal regulation of endogenous H 2 S production together with broader changes in sulfur amino acid (SAA) metabolism with implications for DNA methylation and redox status., Critical Issues: Here, we discuss the role of dietary SAAs and growth hormone (GH)/thyroid hormone (TH) signaling in regulation of endogenous H 2 S production largely via repression of H 2 S generating enzymes cystathionine γ-lyase (CGL) and cystathionine β-synthase (CBS) on the level of gene transcription, as well as reciprocal regulation of GH and TH signaling by H 2 S itself. We also discuss plasticity of CGL and CBS gene expression in response to environmental stimuli and the potential of the microbiome to impact overall H 2 S levels., Future Directions: The relative contribution of increased H 2 S to health span or lifespan benefits in models of extended longevity remains to be determined, as does the mechanism by which such benefits occur. Nonetheless, our ability to control H 2 S levels using exogenous H 2 S donors or by modifying the endogenous H 2 S production/consumption equilibrium has the potential to improve health and increase "shelf-life" across evolutionary boundaries, including our own. Antioxid. Redox Signal. 28, 1483-1502.

Dietary sterols including cholesterol and phytosterols are essential substrates for insect steroid hormone (ecdysteroid) synthesis in the prothoracic glands (PGs). In the silkworm Bombyx mori, one of the model species of insects, the steroidogenesis has been well demonstrated that cholesterol biotransformation into ecdysone in the PG cells. Because insects lack the ability to synthesize cellular sterol de novo, lipoprotein, lipophorin (Lp), has been thought to be the major cholesterol supply source; however, details of cholesterol behavior from Lp to the PG cells has not been analyzed till date. In this report, we developed Lp incorporation method using labeled cholesterols such as 22-NBD-cholesterol and cholesterol-25,26,26,26,27,27,27-d7 (cholesterol-d7), and analyzed the internalization and metabolism of cholesterol in PGs in vitro using the silkworm Bombyx mori. The internalization of cholesterol was visualized using 22-NBD-cholesterol. PGs showed an enriched cellular 22-NBD-cholesterol signal, which dissociated from the Lp localizing at the close area of cell membrane. The distribution pattern observed in the PGs was different from other tissues such as the brain, fat body, and Malpighian tubules, suggesting that the internalization of cholesterol in the PGs was distinct from other tissues. The metabolism of cholesterol was traced using LC-MS/MS methods to detect cholesterol-d7, 7-dehydrocholesterol-d7 (an expected intermediate metabolite), and the final product ecdysone-d6. 7-Dehydrocholesterol-d7 and ecdysone-d6 were detected in the PG culture incubated with labeled Lp, showing that the cholesterol of Lp was utilized for ecdysone synthesis in the PGs. Our results reveal the distinct behavior of cholesterol in the PGs, with the first direct evidence of biochemical fate of lipoprotein cholesterol in insect steroidogenic organ. This will aid in the understanding of the involvement of lipoprotein cholesterol in steroid hormone synthesis in insects., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Recently, the genetic cause of several syndromic forms of glycemia dysregulation has been described. One of them, MEHMO syndrome, is a rare X-linked syndrome recently linked to the EIF2S3 gene mutations. MEHMO is characterized by Mental retardation, Epilepsy, Hypogonadism/hypogenitalism, Microcephaly, and Obesity. Moreover, patients with MEHMO had also diabetes and endocrine phenotype, but detailed information is missing. We aimed to provide more details on the endocrine phenotype in two previously reported male probands with MEHMO carrying a frame-shift mutation (I465fs) in the EIF2S3 gene. Both probands had a neonatal hypoglycemia, early onset insulin-dependent diabetes, and hypopituitarism due to dysregulation and gradual decline of peptide hormone secretion. Based on the clinical course in our two probands and also in previously published patients, neonatal hypoglycemia followed by early-onset diabetes and hypopituitarism may be a consistent part of the MEHMO phenotype.

Purpose of Review: Obesity is currently seen in epidemic proportions globally and is one of the largest contributors to the development of NAFLD. The spectrum of NAFLD, particularly the progressive forms of NASH, is likely to become the leading cause of liver disease in the next decade., Recent Findings: Soluble molecules, encoded by the stomach tissue, have been shown to have pleiotropic effects in both central and peripheral systems involved in energy homeostasis and obesity regulation. As such, the stomach is one of the important players in the complex, multi-system deregulation leading to obesity and NAFLD. The understanding of the stomach tissue as an active endocrine organ that contributes to the signaling milieu leading to the development of obesity and NAFLD is crucial.

It has long been known that the main secretory cells of exocrine and endocrine glands are connected by gap junctions, made by a variety of connexin species that ensure their electrical and metabolic coupling. Experiments in culture systems and animal models have since provided increasing evidence that connexin signaling contributes to control the biosynthesis and release of secretory products, as well as to the life and death of secretory cells. More recently, genetic studies have further provided the first lines of evidence that connexins also control the function of human glands, which are central to the pathogenesis of major endocrine diseases. Here, we summarize the recent information gathered on connexin signaling in these systems, since the last reviews on the topic, with particular regard to the pancreatic beta cells which produce insulin, and the renal cells which produce renin. These cells are keys to the development of various forms of diabetes and hypertension, respectively, and combine to account for the exploding, worldwide prevalence of the metabolic syndrome. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To determine whether adding dehydroepiandrosterone to combined oral contraceptives (COCs) maintains physiological levels of free testosterone., Study Design: A randomized, double-blind, placebo-controlled, two-way crossover study conducted in 81 healthy women (age range: 20-35 years; Body mass index (BMI) range: 18-35 kg/m 2 ) using oral contraceptives. Androgens, sex hormone-binding globulin (SHBG), estradiol (E2) and estrone (E1) were measured, and free testosterone and the free testosterone index were calculated. Subjects discontinued oral contraceptive use for at least one menstrual cycle before being randomized to receive five cycles of ethinyl estradiol (EE) combined with either levonorgestrel (EE/LNG group) or drospirenone (EE/DRSP group) together with either dehydroepiandrosterone (DHEA) (50 mg/day orally) or placebo. Subsequently, all subjects crossed over to the other treatment arm for an additional five cycles., Results: Both COCs decreased the levels of all androgens measured. Significant decreases (p<.05) were found with EE/LNG and EE/DRSP for total testosterone (54.5% and 11.3%, respectively) and for free testosterone (66.8% and 75.6%, respectively). Adding DHEA to the COCs significantly increased all androgens compared to placebo. Moreover, including DHEA restored free testosterone levels to baseline values in both COC groups and total testosterone levels to baseline in the EE/LNG group and above baseline in the EE/DRSP group. SHBG concentrations were significantly higher with EE/DRSP compared to EE/LNG (p<.0001). The addition of DHEA did not affect the levels of SHBG., Conclusions: Taking COCs reduces total and free testosterone levels and increases SHBG concentrations. By coadministration with DHEA, physiological levels of total and free testosterone are restored while using EE/LNG. With EE/DRSP, only the free testosterone level is normalized by DHEA coadministration., Implications: A daily oral dose of 50-mg DHEA maintains physiological free and total testosterone levels in women who are using an EE/LNG-containing COC., (Copyright © 2016 Pantarhei Bioscience. Published by Elsevier Inc. All rights reserved.)

In recent years, long non-coding RNAs (lncRNAs) have attracted the attention of researchers with their involvement in all facets of life. LncRNAs are transcripts of more than 200 nucleotides which lack defined protein coding potential. Although they do not code for proteins, a large number of them are involved in regulating gene expression and translation. The presence of numerous lncRNAs in the human genome has prompted us to investigate the contribution of these molecules to human biology and medicine. In this review, we present the potential role of lncRNAs interlinked to different human diseases and genetic disorders. We also describe their role in cellular differentiation and aging and discuss their potential importance as biomarkers and as therapeutic agents.

Oxytocin regulates a diverse set of processes including stress, analgesia, metabolism, and social behavior. How such diverse functions are mediated by a single hormonal system is not well understood. Different functions of oxytocin could be mediated by distinct cell groups, yet it is currently unknown whether different oxytocinergic cell types exist that specifically mediate peripheral neuroendocrine or various central neuromodulatory processes via dedicated pathways. Using the Brainbow technique to map the morphology and projections of individual oxytocinergic cells in the larval zebrafish brain, we report here the existence of two main types of oxytocinergic cells: those that innervate the pituitary and those that innervate diverse brain regions. Similar to the situation in the adult rat and the adult midshipman, but in contrast to the situation in the adult trout, these two cell types are mutually exclusive and can be distinguished based on morphological and anatomical criteria. Further, our results reveal that complex oxytocinergic innervation patterns are already established in the larval zebrafish brain.

More than 800 different human membrane-spanning G-protein-coupled receptors (GPCRs) serve as signal transducers at biological barriers. These receptors are activated by a wide variety of ligands such as peptides, ions and hormones, and are able to activate a diverse set of intracellular signaling pathways. GPCRs are of central importance in endocrine regulation, which underpins the significance of comprehensively studying these receptors and interrelated systems. During the last decade, the capacity for multimerization of GPCRs was found to be a common and functionally relevant property. The interaction between GPCR monomers results in higher order complexes such as homomers (identical receptor subtype) or heteromers (different receptor subtypes), which may be present in a specific and dynamic monomer/oligomer equilibrium. It is widely accepted that the oligomerization of GPCRs is a mechanism for determining the fine-tuning and expansion of cellular processes by modification of ligand action, expression levels, and related signaling outcome. Accordingly, oligomerization provides exciting opportunities to optimize pharmacological treatment with respect to receptor target and tissue selectivity or for the development of diagnostic tools. On the other hand, GPCR heteromerization may be a potential reason for the undesired side effects of pharmacological interventions, faced with numerous and common mutual signaling modifications in heteromeric constellations. Finally, detailed deciphering of the physiological occurrence and relevance of specific GPCR/GPCR-ligand interactions poses a future challenge. This review will tackle the aspects of GPCR oligomerization with specific emphasis on family A GPCRs involved in endocrine regulation, whereby only a subset of these receptors will be discussed in detail., (© 2016 Society for Endocrinology.)

In decapod crustaceans, arthropod steroid hormones or ecdysteroids regulate molting. These hormones are synthesized and released from a pair of molting glands called the Y-organs (YO). Cyclic nucleotide, mTOR, and TGFβ/Smad signaling pathways mediate molt cycle-dependent phase transitions in the YO. To further identify the genes involved in the regulation of molting, a YO transcriptome was generated from three biological replicates of intermolt blackback land crab, Gecarcinus lateralis. Illumina sequencing of cDNA libraries generated 227,811,829 100-base pair (bp) paired-end reads; following trimming, 90% of the reads were used for further analyses. The trimmed reads were assembled de novo using Trinity software to generate 288,673 contigs with a mean length of 872 bp and a median length of 1842 bp. Redundancy among contig sequences was reduced by CD-HIT-EST, and the output constituted the baseline transcriptome database. Using Bowtie2, 92% to 93% of the reads were mapped back to the transcriptome. Individual contigs were annotated using BLAST, HMMER, TMHMM, SignalP, and Trinotate, resulting in assignments of 20% of the contigs. Functional and pathway annotations were carried out via gene ontology (GO) and KEGG orthology (KO) analyses; 58% and 44% of the contigs with BLASTx hits were assigned to GO and KO terms, respectively. The gene expression profile was similar to a crayfish YO transcriptome database, and the relative abundance of each contig was highly correlated among the three G. lateralis replicates. Signal transduction pathway orthologs were well represented, including those in the mTOR, TGFβ, cyclic nucleotide, MAP kinase, calcium, VEGF, phosphatidylinositol, ErbB, Wnt, Hedgehog, Jak-STAT, and Notch pathways., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Nesfatin-1 was recently identified and introduced as food intake-regulatory hormone. Soon thereafter, mounting evidence indicated a much broader role for nesfatin-1 with an involvement in the regulation of food intake, gastrointestinal motility, glucose homeostasis, blood pressure and stress. Despite the growing knowledge on the physiological regulation and functions of nesfatin-1, the receptor mediating these effects remains to be characterized. Therefore, the aim of this study was to investigate the peripheral and central localization of the nesfatin-1 receptor by autoradiography. Male Sprague-Dawley rats were used and peripheral as well as brain tissue was processed for (125)I-nesfatin-1 autoradiography. In peripheral tissues, an autoradiographic signal was observed in the gastric mucosa of corpus and antrum, in duodenum, jejunum and ileum, while no signal was detected in the colon. Preabsorption of (125)I-nesfatin-1 with non-labeled nesfatin-1 greatly diminished the autoradiographic signal in the stomach indicating specificity (-32%, p < 0.001). A displacement assay showed an effective concentration by which 50% of (125)I-nesfatin-1 bound to the receptor (EC50) in the gastric corpus of 80 pM. Moreover, autoradiography was observed in endocrine tissues including the pituitary, pancreas, adrenal gland, testis and visceral adipose tissue. In addition, also heart, skeletal muscle, lung, liver and kidney showed autoradiographic signals. In the brain, strong (125)I-nesfatin-1 autoradiography was detected in the cortex, paraventricular nucleus of the hypothalamus, area postrema, dorsal motor nucleus of the vagus nerve and cerebellum. Based on the distribution of nesfatin-1 autoradiography, nesfatin-1 is a pleiotropic hormone that is involved in the regulation of several homeostatic functions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Ecdysteroids secreted by the prothoracic gland (PG) cells of insects control the developmental timing of their immature life stages. These cells have been historically considered as carrying out a single function in insects, namely the biochemical conversion of cholesterol to ecdysteroids and their secretion. A growing body of evidence shows that PG cells receive multiple cues during insect development so we tested the hypothesis that they carry out more than just one function in insects. We characterised the molecular nature and developmental profiles of cell membrane receptors in PG cells of Bombyx mori during the final larval stage and determined what receptors decode nutritional, developmental and physiological signals. Through iterative approaches we identified a complex repertoire of cell membrane receptors that are expressed in intricate patterns and activate previously unidentified signal transduction cascades in PG cells. The expression patterns of some of these receptors explain precisely the mechanisms that are known to control ecdysteroidogenesis. However, the presence of receptors for the notch, hedgehog and wingless signalling pathways and the expression of innate immunity-related receptors such as phagocytosis receptors, receptors for microbial ligands and Toll-like receptors call for a re-evaluation of the role these cells play in insects.

Gene duplication and positive selection can be important determinants of the evolution of venom, a protein-rich secretion used in prey capture and defense. In a typical model of venom evolution, gene duplicates switch to venom gland expression and change function under the action of positive selection, which together with further duplication produces large gene families encoding diverse toxins. Although these processes have been demonstrated for individual toxin families, high-throughput multitissue sequencing of closely related venomous species can provide insights into evolutionary dynamics at the scale of the entire venom gland transcriptome. By assembling and analyzing multitissue transcriptomes from the Western black widow spider and two closely related species with distinct venom toxicity phenotypes, we do not find that gene duplication and duplicate retention is greater in gene families with venom gland biased expression in comparison with broadly expressed families. Positive selection has acted on some venom toxin families, but does not appear to be in excess for families with venom gland biased expression. Moreover, we find 309 distinct gene families that have single transcripts with venom gland biased expression, suggesting that the switching of genes to venom gland expression in numerous unrelated gene families has been a dominant mode of evolution. We also find ample variation in protein sequences of venom gland-specific transcripts, lineage-specific family sizes, and ortholog expression among species. This variation might contribute to the variable venom toxicity of these species., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Context: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, characterized by infiltration of foamy histiocytes in multiple organs. Endocrine involvement has mostly been described in case reports., Objective: We performed systematic endocrine evaluation in a large cohort of patients with ECD., Design: This was a single-center observational study conducted between October 2007 and May 2013., Setting: The evaluation was conducted in Pitié-Salpêtrière Hospital (Paris, France), a tertiary care hospital., Patients: Sixty-four consecutive patients with ECD (sex ratio, 3.6; mean age, 57.6 years [range, 20-80 years]). Thirty-six patients had follow-up assessments., Interventions: There were no interventions., Main Outcome Measures: Clinical, biological, and morphological evaluations of pituitary, gonadal, adrenal, and thyroid functions, as well as metabolic evaluation, were performed., Results: Diabetes insipidus was found in 33.3% of patients, frequently as the first manifestation of ECD. Anterior pituitary dysfunction was found in 91.3% of patients with full anterior pituitary evaluation, including somatotropic deficiency (78.6%), hyperprolactinemia (44.1%), gonadotropic deficiency (22.2%), thyrotropic deficiency (9.5%), and corticotropic deficiency (3.1%). Thirty-five patients (54.7%) had ≥2 anterior pituitary dysfunctional axes, rising to 69.6% (16 of 23) when only patients with complete evaluations were considered. Two patients had panhypopituitarism. Infiltration of the pituitary and stalk was found with magnetic resonance imaging in 24.4% of patients. Testicular insufficiency was found in 53.1% of patients, with sonographic testicular infiltration in 29% of men, mostly bilateral. Computed tomography adrenal infiltration was found in 39.1% of patients, and 1 case of adrenal insufficiency was observed. No patient was free of endocrine hormonal or morphological involvement. Endocrine dysfunctions were most often permanent, and new deficits appeared during follow-up., Conclusion: Endocrine involvement is very frequent in ECD and should be evaluated carefully at diagnosis and during follow-up.

Five syndromes share predominantly hyperplastic glands with a primary excess of hormones: neonatal severe primary hyperparathyroidism, from homozygous mutated CASR, begins severely in utero; congenital non-autoimmune thyrotoxicosis, from mutated TSHR, varies from severe with fetal onset to mild with adult onset; familial male-limited precocious puberty, from mutated LHR, expresses testosterone oversecretion in young boys; hereditary ovarian hyperstimulation syndrome, from mutated FSHR, expresses symptomatic systemic vascular permeabilities during pregnancy; and familial hyperaldosteronism type IIIA, from mutated KCNJ5, presents in young children with hypertension and hypokalemia. The grouping of these five syndromes highlights predominant hyperplasia as a stable tissue endpoint and as their tissue stage for all of the hormone excess. Comparisons were made among this and two other groups of syndromes, forming a continuum of gland staging: predominant oversecretions express little or no hyperplasia; predominant hyperplasias express little or no neoplasia; and predominant neoplasias express nodules, adenomas, or cancers. Hyperplasias may progress (5 of 5) to neoplastic stages while predominant oversecretions rarely do (1 of 6; frequencies differ P<0.02). Hyperplasias do not show tumor multiplicity (0 of 5) unlike neoplasias that do (13 of 19; P<0.02). Hyperplasias express mutation of a plasma membrane-bound sensor (5 of 5), while neoplasias rarely do (3 of 14; P<0.002). In conclusion, the multiple distinguishing themes within the hyperplasias establish a robust pathophysiology. It has the shared and novel feature of mutant sensors in the plasma membrane, suggesting that these are major contributors to hyperplasia., (© 2016 Society for Endocrinology.)

Steroid hormones are a large family of cholesterol derivatives regulating development and physiology in both the animal and plant kingdoms, but little is known concerning mechanisms of their secretion from steroidogenic tissues. Here, we present evidence that in Drosophila, endocrine release of the steroid hormone ecdysone is mediated through a regulated vesicular trafficking mechanism. Inhibition of calcium signaling in the steroidogenic prothoracic gland results in the accumulation of unreleased ecdysone, and the knockdown of calcium-mediated vesicle exocytosis components in the gland caused developmental defects due to deficiency of ecdysone. Accumulation of synaptotagmin-labeled vesicles in the gland is observed when calcium signaling is disrupted, and these vesicles contain an ABC transporter that functions as an ecdysone pump to fill vesicles. We propose that trafficking of steroid hormones out of endocrine cells is not always through a simple diffusion mechanism as presently thought, but instead can involve a regulated vesicle-mediated release process., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Biochemical processes initiated by estrogenic hormones in the organs which are not directly related to reproduction were described in the survey on the basis of literature and the authors' own studies. The importance of these compounds in the regulation of fundamental biological processes has been established in the last decades. The biochemical mechanisms of realization of estrogen effects may be considered as potential links of pathogenesis for a number of diseases and as targets of their therapy.

Spexin mRNA and protein are widely expressed in rat tissues and associate with weight loss in rodents of diet-induced obesity. Its location in endocrine and epithelial cells has also been suggested. Spexin is a novel peptide that involves weight loss in rodents of diet-induced obesity. Therefore, we aimed to examine its expression in human tissues and test whether spexin could have a role in glucose and lipid metabolism in type 2 diabetes mellitus (T2DM). The expression of the spexin gene and immunoreactivity in the adrenal gland, skin, stomach, small intestine, liver, thyroid, pancreatic islets, visceral fat, lung, colon, and kidney was higher than that in the muscle and connective tissue. Immunoreactive serum spexin levels were reduced in T2DM patients and correlated with fasting blood glucose (FBG, r=-0.686, P<0.001), hemoglobin A1c (HbA1c, r=-0.632, P<0.001), triglyceride (TG, r=-0.236, P<0.001) and low density lipoprotein-cholesterol (LDL-C, r=-0.382, P<0.001). A negative correlation of blood glucose with spexin was observed during oral glucose tolerance test (OGTT). Spexin is intensely expressed in normal human endocrine and epithelial tissues, indicating that spexin may be involved in physiological functions of endocrine and in several other tissues. Circulating spexin levels are low in T2DM patients and negatively related to blood glucose and lipids suggesting that the peptide may play a role in glucose and lipid metabolism in T2DM., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Combinations of stressors occur regularly throughout an animal's life, especially in agriculture and aquaculture settings. If an animal fails to acclimate to these stressors, stress becomes chronic, and a condition of allostatic overload arises with negative results for animal welfare. In the current study, we describe effects of exposing Atlantic salmon parr to an unpredictable chronic stressor (UCS) paradigm for 3 weeks. The paradigm involves exposure of fish to seven unpredictable stressors three times a day. At the end of the trial, experimental and control fish were challenged with yet another novel stressor and sampled before and 1 h after that challenge. Plasma cortisol decreased steadily over time in stressed fish, indicative of exhaustion of the endocrine stress axis. This was confirmed by a lower cortisol response to the novel stressor at the end of the stress period in chronically stressed fish compared with the control group. In the preoptic area (POA) and pituitary gland, chronic stress resulted in decreased gene expression of 11βhsd2, gr1 and gr2 in the POA and increased expression of those genes in the pituitary gland. POA crf expression and pituitary expression of pomcs and mr increased, whereas interrenal gene expression was unaffected. Exposure to the novel stressor had no effect on POA and interrenal gene expression. In the pituitary, crfr1, pomcs, 11βhsd2, grs and mr were down-regulated. In summary, our results provide a novel overview of the dynamic changes that occur at every level of the hypothalamic-pituitary gland-interrenal gland (HPI) axis as a result of chronic stress in Atlantic salmon., (© 2015. Published by The Company of Biologists Ltd.)