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Endocrinology

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https://read.qxmd.com/read/30901026/acute-suppression-of-lh-secretion-by-prolactin-in-female-mice-is-mediated-by-kisspeptin-neurons-in-the-arcuate-nucleus
#1
Rosemary S E Brown, Zin Khant Aung, Hollian R Phillipps, Zsuzsanna Barad, Hsin-Jui Lein, Ulrich Boehm, Raphael E Szawka, David R Grattan
Hyperprolactinemia causes infertility, but the specific mechanism is unknown. It is clear that elevated prolactin levels suppress pulsatile release of gonadotrophin-releasing hormone (GnRH) from the hypothalamus, with a consequent reduction in pulsatile luteinizing hormone (LH) secretion from the pituitary. Only a few GnRH neurons express prolactin receptors (Prlr), however, and thus prolactin must act indirectly in the underlying neural circuitry. Here, we have tested the hypothesis that prolactin-induced inhibition of LH secretion is mediated by kisspeptin neurons, which provide major excitatory inputs to GnRH neurons...
March 22, 2019: Endocrinology
https://read.qxmd.com/read/30901022/phospho-pr-isoforms-and-cancer-stem-cells-what-does-the-foxo1-say
#2
Lynsey M Fettig, Carol A Sartorius
No abstract text is available yet for this article.
March 22, 2019: Endocrinology
https://read.qxmd.com/read/30892605/chronic-exposure-of-mice-to-bisphenol-a-alters-uterine-fgf-signaling-and-leads-to-aberrant-epithelial-proliferation
#3
Alison M Neff, Sean C Blanco, Jodi A Flaws, Indrani C Bagchi, Milan K Bagchi
Uterine epithelial proliferation is regulated in a paracrine manner by a complex interplay between estrogen (E) and progesterone (P) signaling, wherein E stimulates proliferation and P inhibits it. Perturbation of steroid hormone signaling within the uterine milieu could contribute to the development of endometrial hyperplasia and cancer. It is well established that bisphenol-A (BPA) is an endocrine disrupting chemical with weak estrogenic effects, although little is known about how it impacts steroid hormone signaling in the adult uterus...
March 20, 2019: Endocrinology
https://read.qxmd.com/read/30888399/interactions-between-the-gravitostat-and-the-fibroblast-growth-factor-system-for-the-regulation-of-body-weight
#4
Vilborg Palsdottir, Sara H Windahl, Daniel A Hägg, Hanna Keantar, Jakob Bellman, Andrew Buchanan, Tristan J Vaughan, Daniel Lindén, John-Olov Jansson, Claes Ohlsson
Both fibroblast growth factors (FGFs), by binding to FGF receptors, and activation of the gravitostat, by artificial loading, decrease the body weight. Previous studies demonstrate that both the FGF system and loading have the capacity to regulate body weight independently of leptin. The aim of the present study was to determine the possible interactions between the effect of increased loading and the FGF system for the regulation of body weight. We observed that the body weight reducing effect of increased loading was abolished in mice treated with a monoclonal antibody directed against FGFR1c, suggesting interactions between the two systems...
March 19, 2019: Endocrinology
https://read.qxmd.com/read/30882881/mst-kinases-and-metabolism
#5
Celia M Pombo, Cristina Iglesias, Miriam Sartages, Juan B Zalvide
Since the discovery of the MST kinase family of proteins (MST1/STK4, MST2/STK3, MST3/STK24 and SOK1/STK25), much has been done that adds to our knowledge of their structure, regulation and function. In the last few years, a series of articles have unveiled a previous unknown relation of these kinases with metabolic regulation and the homeostasis of metabolic tissues. The aim of this review is to bring together this body of data to have a detailed picture of the current knowledge related with these proteins, metabolism, and some of its associated diseases...
March 18, 2019: Endocrinology
https://read.qxmd.com/read/30874792/ghrelin-s-relationship-to-blood-glucose
#6
Bharath K Mani, Kripa Shankar, Jeffrey M Zigman
Much effort has been directed at studying the orexigenic actions of administered ghrelin and the potential effects of the endogenous ghrelin system on food intake, food reward, body weight, adiposity, and energy expenditure. Although endogenous ghrelin's actions on some of these processes remain ambiguous, its glucoregulatory actions have emerged as well-recognized features during extreme metabolic conditions. The blood glucose-raising actions of ghrelin are beneficial during starvation-like conditions, defending against life-threatening falls in blood glucose, but are seemingly detrimental in obese states and in certain monogenic forms of diabetes, contributing to hyperglycemia...
March 15, 2019: Endocrinology
https://read.qxmd.com/read/30874767/the-activin-social-network-activin-inhibin-and-follistatin-in-breast-development-and-cancer
#7
Darcie D Seachrist, Ruth A Keri
Activins and inhibins are closely related protein heterodimers with similar tissue distribution, yet these two complexes have opposing functions in development and disease. Both are secreted cytokine hormones, with activin being the primary inducer of downstream signaling cascades and inhibin acting as a rheostat that exquisitely governs activin function. Adding to the complexity of activin signaling, follistatin, a high glycosylated monomeric protein, binds activin with high affinity, also restraining downstream pathway activation but through a mechanism distinct from that of inhibin...
March 15, 2019: Endocrinology
https://read.qxmd.com/read/30874725/how-pulsatile-kisspeptin-stimulation-and-gnrh-autocrine-feedback-can-drive-gnrh-secretion-a-modeling-investigation
#8
Jonas Lehnert, Anmar Khadra
Pulsatile secretion of gonadotropin-releasing hormone (GnRH) from hypothalamic GnRH neurons tightly regulates the release of mammalian reproductive hormones. While key factors such as electrical activity and stimulation by kisspeptin have been extensively studied, the underlying mechanisms that regulate GnRH release are still not fully understood. Previously developed mathematical models studied hormonal release and electrical properties of GnRH neurons separately, but never integrated both components. Here we present a more complete biophysical model to investigate how electrical activity and hormonal release interact...
March 15, 2019: Endocrinology
https://read.qxmd.com/read/30840070/sex-biased-lncrnas-inversely-correlate-with-sex-opposite-gene-co-expression-networks-in-diversity-outbred-mouse-liver
#9
Tisha Melia, David J Waxman
Sex differences in liver gene expression are determined by pituitary growth hormone secretion patterns, which regulate sex-dependent liver transcription factors and establish sex-specific chromatin states. Hypophysectomy (hypox) identifies two major classes of liver sex-biased genes, defined by their sex-dependent positive or negative responses to pituitary hormone ablation; however, the mechanisms that underlie each hypox-response class are unknown. Here, we sought to discover candidate regulatory long noncoding RNAs (lncRNAs) controlling responsiveness to hypophysectomy...
March 6, 2019: Endocrinology
https://read.qxmd.com/read/30840056/suppression-of-leptin-transport-into-the-brain-contributes-to-leptin-resistance-during-pregnancy-in-the-mouse
#10
Papillon Gustafson, Sharon R Ladyman, Rosemary S E Brown
During pregnancy, when both food intake and circulating leptin concentrations increase, the brain becomes insensitive to leptin. The mechanism by which central leptin resistance during pregnancy emerges remains poorly understood. We investigated whether structural changes in the blood brain barrier (BBB) or changes in carrier-mediated transport of leptin into the brain might contribute to pregnancy-induced leptin resistance. Immunohistochemical evaluation of the BBB at the level of the arcuate nucleus and median eminence in virgin, pregnant and lactating mice was undertaken by labelling for tanycytes (vimentin), tight junction protein (zona occludens-1), and a marker of fenestrated endothelial capillaries (MECA-32)...
March 6, 2019: Endocrinology
https://read.qxmd.com/read/30830222/androgens-ameliorate-impaired-ischemia-induced-neovascularization-due-to-aging-in-male-mice
#11
Yuen Ting Lam, Laura Lecce, Sui Ching Yuen, Steven G Wise, David J Handelsman, Richard H Karas, Martin K C Ng
There is abundant evidence that low circulating testosterone levels in older men is associated with adverse cardiovascular outcomes, however, the direction of causality is unclear. Although there is a burgeoning interest in the potential of androgen therapy in older men, the effect of androgens on cardiovascular regeneration in aging males remains poorly defined. We investigated the role of androgens in age-related impairment in ischemia-induced neovascularization. Castrated young (2-month) and old (24-month) male mice were subjected to unilateral hindlimb ischemia and treated with subdermal dihydrotestosterone (DHT) or placebo silastic implants...
March 4, 2019: Endocrinology
https://read.qxmd.com/read/30822353/regulation-of-somatostatin-receptor-2-trafficking-by-c-tail-motifs-and-the-retromer
#12
Courtney Olsen, Kimiya Memarzadeh, Arzu Ulu, Heather S Carr, Andrew J Bean, Jeffrey A Frost
The Gi-coupled somatostatin receptor 2 (SST2) is a G-protein coupled receptor (GPCR) that mediates many of somatostatin's neuroendocrine actions. Upon stimulation, SST2 is rapidly internalized and transported to early endosomes before being recycled to the plasma membrane. However, little is known about the intracellular itinerary of SST2 after it moves to the early endosomal compartment, or the cytoplasmic proteins that regulate its trafficking. As Postsynaptic density protein/Discs large-1/Zona occludens-1 (PDZ) domain interactions often regulate the trafficking and signaling potential of other GPCRs, we examined the role of the SST2 PDZ ligand and additional C-terminal residues in controlling its intracellular trafficking...
March 1, 2019: Endocrinology
https://read.qxmd.com/read/30822352/a-modifying-autoantigen-in-graves-disease
#13
Rauf Latif, Mihaly Mezei, Syed A Morshed, Risheng Ma, Rachel Ehrlich, Terry F Davies
The TSH receptor (TSHR) is the major autoantigen in Graves' disease (GD). Bioinformatic analyses predicts the existence of several human TSHR isoforms from alternative splicing which can lead to the co-expression of multiple receptor forms of which the most abundant is TSHR-v1.3. In-silico modeling of TSHR v1.3 demonstrated the structural integrity of this truncated receptor isoform and its potential binding of TSH. Tissue profiling revealed wide expression of TSHRv1.3 with a predominant presence in thyroid, bone marrow, thymus and adipose tissue...
March 1, 2019: Endocrinology
https://read.qxmd.com/read/30811529/nadph-oxidase-nox-mediates-membrane-androgen-receptor-induced-neurodegeneration
#14
Mavis A A Tenkorang, Phong Duong, Rebecca L Cunningham
Oxidative stress (OS) is a common characteristic of several neurodegenerative disorders, including Parkinson's disease (PD). PD is more prevalent in men than women, indicating the possible involvement of androgens. Androgens can have either neuroprotective or neurodamaging effects, depending on the presence of OS. Specifically, in an OS environment, androgens via a membrane-associated androgen receptor (mAR) exacerbate OS-induced damage. To investigate the role of androgens on OS signaling and neurodegeneration, the effects of testosterone and androgen receptor activation on the major OS signaling cascades, NADPH Oxidase 1/2 (NOX1, NOX2) and Gαq/InsP3R, were examined...
February 27, 2019: Endocrinology
https://read.qxmd.com/read/30807635/nod1-an-interface-between-innate-immunity-and-insulin-resistance
#15
Sydney L Rivers, Amira Klip, Adria Giacca
Insulin resistance is driven, in part, by activation of the innate immune system. Here we discuss evidence linking nucleotide-binding oligomerization domain-1 (NOD1), an intracellular pattern recognition receptor, to the onset and progression of obesity-induced insulin resistance. On a molecular level, crosstalk between downstream NOD1 effectors and the insulin receptor pathway inhibits insulin signalling, potentially through reduced Insulin Receptor Substrate (IRS) action. In vivo studies demonstrate that NOD1 activation induces peripheral, hepatic and whole-body insulin resistance, while NOD1-deficient models are protected from high fat diet (HFD)-induced insulin resistance...
February 26, 2019: Endocrinology
https://read.qxmd.com/read/30802285/pegylated-human-leptin-d23l-mutant-preparation-and-biological-activity-in-vitro-and-in-vivo-in-male-ob-ob-mice
#16
Arieh Gertler, Gili Solomon
Recombinant monomeric human leptin (hLEP) and its D23L mutant were prepared in Escherichia coli and pegylated at their N-terminus using methoxy PEG-propionaldehyde 20 kDa. As determined by both SDS-PAGE and size-exclusion chromatography, the pegylated proteins consisted of >90% mono-pegylated and less than 10% of double-pegylated species. Circular dichroism spectra showed that their secondary structure, characteristic of all four α-helix bundle cytokines, was not affected by either the D23L mutation or pegylation...
February 25, 2019: Endocrinology
https://read.qxmd.com/read/30802283/fibroblast-growth-factor-21-controls-dietary-protein-intake-in-male-mice
#17
Karlton R Larson, Aki T-B Chaffin, Michael L Goodson, Yanbin Fang, Karen K Ryan
Whereas carbohydrates and lipids are stored as glycogen and fat, there is no analogous inert storage form of protein. Therefore, continuous adjustments in feeding behavior are needed to match amino acid supply to ongoing physiologic need. Neuroendocrine mechanisms facilitating this behavioral control of protein and amino acid homeostasis remain unclear. The hepatokine FGF21 is well-positioned for such a role, since it is robustly secreted in response to protein and/or amino acid deficit. Here we tested the hypothesis that FGF21 feeds back at its receptors in the nervous system, to shift macronutrient selection towards protein...
February 25, 2019: Endocrinology
https://read.qxmd.com/read/30802281/leptin-receptor-signaling-in-sim1-expressing-neurons-regulates-body-temperature-and-adaptive-thermogenesis
#18
Isin Cakir, Myriam Diaz Martinez, Pauline Lining Pan, E Brian Welch, Sachin Patel, Masoud Ghamari-Langroudi
Leptin signals to regulate food intake and energy expenditure under conditions of normative energy homeostasis. The central expression and function of leptin receptor B (LepRb) have been extensively studied over the past two decades; however, the mechanisms by which LepRb signaling dysregulation contributes to the pathophysiology of obesity remains unclear. The paraventricular nucleus of the hypothalamus (PVN) plays a crucial role in regulating energy balance as well as the neuroendocrine axes. The role of LepRb expression in the PVN in regard to the regulation of physiological function of leptin has been controversial...
February 25, 2019: Endocrinology
https://read.qxmd.com/read/30794724/the-metabolic-abnormalities-of-chronic-high-dose-glucocorticoids-are-not-mediated-by-hypothalamic-agrp-in-male-mice
#19
Charlotte Sefton, Alison Davies, Tiffany-Jayne Allen, Jonathan R Wray, Rosemary Shoop, Antony Adamson, Neil Humphreys, Anthony P Coll, Anne White, Erika Harno
Glucocorticoids (Gcs) are potent and widely used medicines, but often cause metabolic side effects. A murine model of corticosterone (Cort) treatment results in increased hypothalamic expression of the melanocortin antagonist AgRP in parallel with obesity and hyperglycaemia. This study investigates how these adverse effects develop over time with particular emphasis on hypothalamic involvement. Wild type and Agrp-/- male mice were treated with Cort for three weeks. Phenotypic, biochemical, protein and mRNA analysis was undertaken on central and peripheral tissues including white and brown adipose tissue, liver and muscle to determine the metabolic consequences...
February 22, 2019: Endocrinology
https://read.qxmd.com/read/30776303/mice-missing-cnr1-and-cnr2-show-implantation-defects
#20
Yingju Li, Fenghua Bian, Xiaofei Sun, Sudhansu K Dey
Cannabinoid/endocannabinoid signaling is primarily mediated by CB1 (encoded by Cnr1) and/or CB2 (encoded by Cnr2). Here we show that Cnr1-/-Cnr2-/- mice are subfertile due to compromised implantation. Upon implantation, the epithelium is smooth and adhered to the blastocyst trophectoderm within the implantation chamber (crypt) in wild type mice, whereas the epithelium in Cnr1-/-Cnr2-/- mice is ruffled which compromises appropriate blastocyst-uterine interactions. The suboptimal implantation leads to higher incidence of pregnancy failure in Cnr1-/-Cnr2-/- mice...
February 18, 2019: Endocrinology
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