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Endocrinology

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https://www.readbyqxmd.com/read/28531318/agrp-expressing-adrenal-chromaffin-cells-are-involved-in-the-sympathetic-response-to-fasting
#1
Rajesh Gupta, Yunbing Ma, Manqi Wang, Matthew D Whim
Fasting evokes a homeostatic response that maintains circulating levels of energy-rich metabolites and increases the drive to eat. Centrally this reflex activates a small population of hypothalamic neurons that are characterized by the expression of AgRP, a neuropeptide with an extremely restricted distribution. Apart from the hypothalamus the only other site with significant expression is the adrenal gland but there is disagreement about which cells synthesize AgRP. Using immunohistochemistry, flow cytometry and RT-PCR we show AgRP is present in the mouse adrenal medulla and is expressed by neuroendocrine chromaffin cells that also synthesize the catecholamines and neuropeptide Y...
May 22, 2017: Endocrinology
https://www.readbyqxmd.com/read/28531316/a-comprehensive-method-to-quantify-adaptations-by-male-and-female-mice-with-hot-flashes-induced-by-the-neurokinin-b-receptor-agonist-senktide
#2
Ashley A Krull, Sarah A Larsen, Donald K Clifton, Genevieve Neal-Perry, Robert A Steiner
Vasomotor symptoms (VMS, or hot flashes) plague millions of reproductive age men and women who have natural or iatrogenic loss of sex steroid production. Many affected individuals are left without treatment options because of contraindications to hormone replacement therapy and the lack of equally effective non-hormonal alternatives. Moreover, development of safer, more effective therapies has been stymied by the lack of an animal model that recapitulates the hot flash phenomenon and enables direct testing of hypotheses regarding the pathophysiology underlying hot flashes...
May 22, 2017: Endocrinology
https://www.readbyqxmd.com/read/28525638/glucokinase-gene-may-be-a-more-suitable-target-than-the-insulin-gene-for-detection-of-beta-cell-death
#3
J Sklenarova, L Petruzelkova, S Kolouskova, J Lebl, Z Sumnik, O Cinek
Detection and quantification of unmethylated circulating insulin (INS) DNA presumably released from beta cells has been previously used for assessing their destruction. As the targets within the INS gene suffer from suboptimal specificity, we sought to improve the assay parameters by using the glucokinase gene (GCK) tissue-specific pancreatic promoter.The amount of methylated and unmethylated GCK DNA was measured using a droplet PCR assay, and compared with the previously published INS-targeted assay. The method was tested using synthetic target sequences and DNA from pancreatic islets, blood, brain, kidney, large intestine, liver, lung, small intestine and stomach...
May 18, 2017: Endocrinology
https://www.readbyqxmd.com/read/28525591/f4-80-macrophages-contribute-to-clearance-of-senescent-cells-in-the-mouse-postpartum-uterus
#4
Mahiro Egashira, Yasushi Hirota, Ryoko Shimizu-Hirota, Tomoko Saito-Fujita, Hirofumi Haraguchi, Leona Matsumoto, Mitsunori Matsuo, Takehiro Hiraoka, Tomoki Tanaka, Shun Akaeda, Chiaki Takehisa, Mayuko Saito-Kanatani, Kei-Ichiro Maeda, Tomoyuki Fujii, Yutaka Osuga
Cellular senescence, defined as an irreversible cell cycle arrest, exacerbates tissue microenvironment. Our previous study demonstrated that mouse uterine senescent cells are physiologically increased according to gestational days and their abnormal accumulation is linked to the onset of preterm delivery. We hypothesized that there is a mechanism for removal of senescent cells after parturition to maintain uterine function. In the current study, we noted abundant uterine senescent cells and their gradual disappearance in the wild-type postpartum mice...
May 18, 2017: Endocrinology
https://www.readbyqxmd.com/read/28520923/decrease-in-expression-of-hoxa10-in-the-decidua-after-embryo-implantation-promotes-trophoblast-invasion
#5
Geeta Godbole, Pankaj Suman, Ankita Malik, Mosami Galvankar, Niraj Joshi, Asgerally Fazleabas, Satish Kumar Gupta, Deepak Modi
A central step towards successful pregnancy involves invasion of the trophoblast cells into the decidua for placentation. Herein, we show that in the human and baboon decidua, HOXA10 expression is downregulated post-implantation and this reduction is most prominent in the decidual cells juxtaposed to the invading placental villi. Intriguingly, the supernatants derived from HOXA10 depleted human decidual cells increase the invasiveness of the trophoblast cell lines ACH-3P and JEG3 in vitro; this increase is due to higher expression and activity of matrix metalloproteases (MMPs) and reduced expression of tissue inhibitors of MMPs (TIMPs) in both the cell lines...
May 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28520870/defining-the-role-of-estrogen-receptor-beta-in-the-regulation-of-female-fertility
#6
Ma Karim Rumi, Prabhakar Singh, Katherine F Roby, Xiao Zhao, Khursheed Iqbal, Anamika Ratri, Tianhua Lei, Wei Cui, Shaon Borosha, Pramod Dhakal, Kaiyu Kubota, Damayanti Chakraborty, Jay L Vivian, Michael W Wolfe, Michael J Soares
Estrogens are essential hormones for the regulation of fertility. Cellular responses to estrogens are mediated by estrogen receptor alpha (ESR1) and estrogen receptor beta (ESR2). In mouse and rat models, disruption of Esr1 causes infertility in both males and females. However, the role of ESR2 in reproductive function remains undecided due to a wide variation in phenotypic observations among Esr2 mutant mouse strains. Regulatory pathways independent of ESR2 binding to its cognate DNA response element have also been implicated in ESR2 signaling...
May 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28510653/chronic-corticosterone-treatment-during-adolescence-has-significant-effects-on-metabolism-and-skeletal-development-in-male-c57bl6-n-mice
#7
Scott A Kinlein, Ziasmin Shahanoor, Russell D Romeo, Ilia N Karatsoreos
Glucocorticoids are potent modulators of metabolic and behavioral function. Their role as mediators in the "stress response" is well known, but arguably their primary physiological function is in the regulation of cellular and organismal metabolism. Disruption of normal glucocorticoid function is linked to metabolic disease, such as Cushing's syndrome. Glucocorticoids are also elevated in many forms of obesity, suggesting that there are bidirectional effects of these potent hormones on metabolism and metabolic function...
May 15, 2017: Endocrinology
https://www.readbyqxmd.com/read/28505239/foxo1-promotes-mitophagy-in-the-podocytes-of-diabetic-male-mice-via-the-pink1-parkin-pathway
#8
Wen Li, Mengmeng Du, Qingzhu Wang, Xiaojun Ma, Lina Wu, Feng Guo, Hongfei Ji, Fengjuan Huang, Guijun Qin
We recently showed that Forkhead-box class O1 (FoxO1) activation protects against high glucose-induced injury by preventing mitochondrial dysfunction in the rat kidney cortex. In addition, FoxO1 has been reported to mediate PINK1 transcription and promote autophagy in response to mitochondrial oxidative stress in murine cardiomyocytes. In this study, we ascertained whether over-expressing FoxO1 in the kidney cortex reverses pre-established diabetic nephropathy in animal models. The effect of FoxO1 on mitophagy signaling pathways was evaluated in mouse podocytes...
May 12, 2017: Endocrinology
https://www.readbyqxmd.com/read/28498971/deletion-of-rhoa-in-progesterone-receptor-expressing-cells-leads-to-luteal-insufficiency-and-infertility-in-female-mice
#9
Ahmed E El Zowalaty, Rong Li, Yi Zheng, John P Lydon, Francesco J DeMayo, Xiaoqin Ye
RhoA is widely expressed throughout the female reproductive system. To assess its role in progesterone receptor (Pgr) expressing cells, we generated RhoA conditional knockout mice RhoAd/d (RhoAf/f-Pgr-Cre+/-). RhoAd/d females had comparable mating activity, serum LH, prolactin, and estradiol levels and ovulation with control but were infertile with progesterone insufficiency, indicating impaired steroidogenesis in RhoAd/d corpus luteum (CL). RhoA was highly expressed in wild type luteal cells and conditionally deleted in RhoAd/d CL...
May 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28498917/the-new-genomics-what-molecular-databases-can-tell-us-about-human-population-variation-and-endocrine-disease
#10
Peter Rotwein
Major recent advances in genetics and genomics present unique opportunities for enhancing our understanding of human physiology and disease predisposition. Here I demonstrate how analysis of genomic information can provide new understanding of endocrine systems, using the human growth hormone (GH) signaling pathway as an illustrative example. GH is essential for normal postnatal growth in children, and plays important roles in other biological processes throughout life. GH actions are mediated by the GH receptor, primarily via the JAK2 protein tyrosine kinase and the STAT5B transcription factor, and inactivating mutations in this pathway all lead to impaired somatic growth...
May 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28498916/effects-of-the-activations-of-three-major-hepatic-akt-substrates-on-glucose-metabolism-in-male-mice
#11
Gota Sakai, Ikuo Inoue, Tokuko Suzuki, Takashi Sumita, Kouichi Inukai, Shigehiro Katayama, Takuya Awata, Tetsuya Yamada, Tomoichiro Asano, Hideki Katagiri, Mitsuhiko Noda, Akira Shimada, Hiraku Ono
Insulin suppresses glucose output from the liver via Akt activation, but which substrate of Akt plays the major role in transducing this effect is unclear. Herein, we postnatally expressed Akt-unresponsive, constitutively-active mutants of three major Akt substrates which are widely considered to regulate glucose metabolism, i.e. FoxO1, PGC-1α and GSK-3β, employing adenoviral gene delivery to the mouse liver. We performed physiological hyperinsulinemic-euglycemic clamp studies using these mice under awake and non-restrained conditions with blood sampling from an arterial catheter...
May 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28486616/the-role-of-vitamin-d-in-the-prevention-of-type-2-diabetes-to-d-or-not-to-d
#12
Edith Angellotti, Anastassios G Pittas
Evidence on biological plausibility from mechanistic studies and highly consistent data from observational studies raise the possibility that optimizing vitamin D status may reduce risk of type 2 diabetes. However, the observational nature of cohort studies precludes a definitive assessment of cause and effect because residual confounding or reverse causation cannot be excluded. Confounding is especially problematic with studies of vitamin D because blood 25-hydoxyvitamin D concentration is not only an excellent biomarker of vitamin D status, reflecting intake or biosynthesis, but also an excellent marker of good overall health...
May 8, 2017: Endocrinology
https://www.readbyqxmd.com/read/28486603/clinical-identification-of-oncogenic-drivers-and-copy-number-alterations-in-pituitary-tumors
#13
Wenya Linda Bi, Noah F Greenwald, Shakti H Ramkissoon, Malak Abedalthagafi, Shannon M Coy, Keith L Ligon, Yu Mei, Laura MacConaill, Matt Ducar, Le Min, Sandro Santagata, Ursula B Kaiser, Rameen Beroukhim, Edward R Laws, Ian F Dunn
Pituitary tumors are the second most common adult primary brain tumor, with a variable clinical course. Recent work has identified a number of genetic determinants of pituitary tumor subtypes, which may augment classic histopathologic classification schemes. We sought to determine whether pituitary tumors could be stratified based on objective molecular characteristics using a clinical genomics assay. We profiled pituitary tumors using OncoPanel, a clinical multiplexed next-generation sequencing assay and retrospectively collected the clinical information and sequencing results for 127 patients from 2012-2016 at the Brigham and Women's Hospital...
May 8, 2017: Endocrinology
https://www.readbyqxmd.com/read/28475811/ablation-of-hepatic-production-of-the-acid-labile-subunit-in-the-bovine-gh-transgenic-mice-effects-on-organ-and-skeletal-growth
#14
Zhongbo Liu, Tianzhen Han, Shannon Fishman, James Butler, Tracy Zimmermann, Frederic Tremblay, Carole Harbison, Nidhi Agrawal, John J Kopchick, Mitchell B Schaffler, Shoshana Yakar
Growth hormone (GH) and insulin like growth factor-1 (IGF-1) are anabolic hormones that facilitate somatic and skeletal growth, and regulate metabolism via endocrine and autocrine/paracrine mechanisms. We hypothesized that excess tissue production of GH will protect skeletal growth and integrity in states of reductions in serum IGF-1 levels. To test our hypothesis we used the bovine GH (bGH) transgenic mice as a model of GH hypersecretion and ablated the liver-derived acid labile subunit (ALS), which stabilizes IGF-1 complexes with IGF-binding protein-3 (IGFBP-3) and -5 in circulation...
May 4, 2017: Endocrinology
https://www.readbyqxmd.com/read/28475692/central-rfrp-3-stimulates-lh-secretion-in-male-mice-and-has-cycle-stage-dependent-inhibitory-effects-in-females
#15
Caroline Ancel, Megan A Inglis, Greg M Anderson
RFamide-related peptide-3 (RFRP-3) is a neuropeptide that is thought to play an inhibitory role in the regulation of reproduction in various mammalian species, although some stimulatory effects have been reported. To date, the effects of RFRP-3 on gonadotropin secretion have been scarcely studied in mice. The aim of the current study was to characterise the effect of RFRP-3 administration on gonadotropin secretion in male and female mice. Adult intact and castrated male mice received acute central injections of 0...
May 4, 2017: Endocrinology
https://www.readbyqxmd.com/read/28472467/hypothalamic-regulation-of-liver-and-muscle-nutrient-partitioning-by-brain-specific-carnitine-palmitoyltransferase-1c-cpt1c-in-male-mice
#16
Macarena Pozo, Rosalía Rodríguez-Rodríguez, Sara Ramírez, Patricia Seoane-Collazo, Miguel López, Dolors Serra, Laura Herrero, Núria Casals
Carnitine palmitoyltransferase 1C (CPT1C), a brain-specific protein localized in the endoplasmic reticulum of neurons, is expressed in almost all brain regions. Based on global knockout (KO) models, CPT1C has demonstrated relevance in hippocampus-dependent spatial learning as well as in hypothalamic regulation of energy balance. Specifically, it has been shown that CPT1C is protective against high-fat diet-induced obesity (DIO), and that CPT1C KO mice show reduced peripheral fatty acid oxidation (FAO) both during fasting and DIO...
May 3, 2017: Endocrinology
https://www.readbyqxmd.com/read/28472300/interaction-of-the-mineralocorticoid-receptor-with-rack1-and-its-role-in-aldosterone-signaling
#17
Maniselvan Kuppusamy, Elise P Gomez-Sanchez, Lauren N Beloate, Maria Plonczynski, Aniko Naray-Fejes-Toth, Geza Fejes-Toth, Celso E Gomez-Sanchez
The mineralocorticoid receptor (MR) is a member of the steroid-thyroid hormone receptor superfamily of ligand-dependent transcription factors with diverse functions including the biological actions of aldosterone. Identification of the various transcriptional co-regulators of MR is essential for understanding the complexity of MR signaling pathways under physiological and pathological conditions. We used a yeast two-hybrid system to find proteins that interact with a full-length MR and found, among other proteins, that MR interacted specifically with Receptor for Activated C Kinase 1 (RACK1), a scaffolding protein...
May 2, 2017: Endocrinology
https://www.readbyqxmd.com/read/28472309/impact-on-experimental-colitis-of-vitamin-d-receptor-deletion-in-intestinal-epithelial-or-myeloid-cells
#18
Carlien Leyssens, Lieve Verlinden, Gert De Hertogh, Shigeaki Kato, Conny Gysemans, Chantal Mathieu, Geert Carmeliet, Annemieke Verstuyf
Inflammatory bowel diseases are gastrointestinal diseases including Crohn's disease and ulcerative colitis. The chronic inflammation is thought to result from an excessive inflammatory response to environmental factors such as luminal bacteria in genetically predisposed individuals. Studies revealed that mice with impaired vitamin D signaling are more susceptible to experimental colitis. To better understand the contribution of vitamin D signaling in different cells of the gut to this disease, we investigated the effects of intestinal-specific or myeloid vitamin D receptor deletion...
May 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28472304/thyroid-hormone-signaling-pathways-time-for-a-more-precise-nomenclature
#19
Frédéric Flamant, Sheue-Yann Cheng, Anthony N Hollenberg, Lars C Moeller, Jacques Samarut, Fredric E Wondisford, Paul M Yen, Samuel Refetoff
Current literature makes a distinction between two pathways for thyroid hormone signaling: genomic and non-genomic. However this classification is a source of confusion. We propose a clarification in the nomenclature which may help to avoid unproductive controversies and favor research progress in this field of research. Four types of thyroid hormone signaling are defined, and the experimental criteria for classification are discussed.
May 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28460125/how-protein-kinase-a-activates-canonical-tyrosine-kinase-signaling-pathways-to-promote-granulosa-cell-differentiation
#20
Nathan C Law, Elyse M Donaubauer, Anthony J Zeleznik, Mary Hunzicker-Dunn
Protein kinase A (PKA) has recently been shown to mimic the actions of follicle-stimulating hormone (FSH) by activating signaling pathways that promote granulosa cell (GC) differentiation, such as phosphatidylinositol 3-kinase (PI3K) and mitogen activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK). We sought to elucidate the mechanism by which PKA, a Ser/Thr kinase, intersected the PI3K/AKT and MAPK/ERK pathways that are canonically activated by receptor tyrosine kinases (RTKs). Our results show that for both of these pathways, the RTK is active in the absence of FSH yet signaling down the pathways to commence transcriptional responses requires FSH-stimulated PKA activation...
April 28, 2017: Endocrinology
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