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Shannon B Z Stephens, Noelia P Di Giorgio, Reanna B Liaw, Ruby A Parra, Jennifer A Yang, Navdeep Chahal, Victoria A Lux-Lantos, Alexander S Kauffman
Kisspeptin, encoded by Kiss1, activates reproduction by stimulating GnRH neurons. Though most Kiss1 neurons are located in the hypothalamus, smaller Kiss1 populations also reside in the MeA, BnST, and LS. However, very little is known about the regulation and function of these extra-hypothalamic Kiss1 neurons. This study focused on the roles and interactions of two signaling factors, E2 and GABA, known to stimulate and inhibit, respectively, extra-hypothalamic Kiss1 expression. First, using ERKO and BERKO mice, we demonstrated that Kiss1 in both the BnST and LS is stimulated by E2, as occurs in the MeA, and that this E2 upregulation occurs via ERα, but not ERβ...
August 9, 2018: Endocrinology
Natalie R Peer, Sze Ming Law, Brenda Murdoch, Eugenia H Goulding, Edward M Eddy, Kwanhee Kim
Retinoic acid receptor alpha (RARA), a retinoic acid-dependent transcription factor, is expressed in both somatic and germ cells of the testis. Rara-null male mice with global Rara mutations displayed severely degenerated testis and infertility phenotypes. To elucidate the specific responsibility of germ cell RARA in spermatogenesis, Rara was deleted in germ cells, generating germ cell-specific Rara conditional knockout (Rara cKO) mice. These Rara cKO animals exhibited phenotypes of quantitatively reduced epididymal sperm counts and disorganized germ cell layers in the seminiferous tubules, which worsened with aging...
August 6, 2018: Endocrinology
Lotta Jansson, Kathleen Vrolix, Andrea Jahraus, Keith F Martin, David C Wraith
We have combined MHC binding assays with immunization and tolerance induction experiments in HLA-DR3 transgenic mice in order to design apitopes (Antigen Processing Independent epiTOPES) derived from TSHR for treatment of patients with Graves' disease (GD). A challenge model was created by using an adenovirus expressing part of the extracellular domain of the thyrotropin receptor (TSHR289). This model was used to test whether current drug treatments for GD would impact on effective antigen-specific immunotherapy using the apitope approach...
August 6, 2018: Endocrinology
Nicolae Ghinea
Improved molecular understanding of tumor microenvironment has resulted in the identification of various cancer cell targets for diagnostic and therapeutic interventions, including the receptor for the follicle-stimulating hormone (FSH), a glycoprotein hormone responsible for growth, maturation and function of human reproductive system. The expression and localization of the FSHR-protein were associated with the tumor epithelial cells and/or with the peripheral tumor blood vessels. The available evidence indicates that in ovarian cancer, prostate cancer, and breast cancer, the tumor epithelial FSHR promotes proliferation, migration and invasion of cancer cells...
August 2, 2018: Endocrinology
Ketan Shrestha, Rina Meidan
During the periovulatory period the profile of FGF2 coincides with elevated PGE2 levels. We investigated therefore whether PGE2 can directly stimulate FGF2 production in bovine granulosa cells and if so, which PTGER type and signaling cascades are involved. We found that PGE2 temporally stimulated FGF2. Accordingly, endoperoxide-synthase2-silenced cells, exhibiting low endogenous PGE2 levels, had reduced FGF2. Furthermore, elevation of viable granulosa cell numbers by PGE2 was abolished with FGF2 receptor1 inhibitor, suggesting that FGF2 mediates this action of PGE2...
July 31, 2018: Endocrinology
Daniel Ferguson, Mitchell Blenden, Irina Hutson, Yingqiu Du, Charles A Harris
The global obesity epidemic is fueling alarming rates of diabetes, associated with increased risk of cardiovascular disease and cancer. Leptin is a hormone secreted by adipose tissue that is a key regulator of body weight and energy expenditure. Leptin-deficient humans and mice are obese, diabetic, infertile, and have hepatic steatosis. While leptin replacement therapy can rescue the pathologies seen in leptin-deficient patients and mouse models, treatment is very costly and requires daily injections. Since adipocytes are the source of leptin secretion we investigated whether mouse embryonic fibroblasts (MEFs), capable of forming adipocytes, could be injected into ob/ob mice and prevent the metabolic phenotype seen in these leptin-deficient mice...
July 31, 2018: Endocrinology
Mone Zaidi, Daria Lizneva, Se-Min Kim, Li Sun, Jameel Iqbal, Maria I New, Clifford J Rosen, Tony Yuen
The Study of Women's Health Across the Nation (SWAN) has taught us that impending ovarian failure during the late perimenopause is associated with a sharp rise in serum FSH, which coincides with the most rapid rate of bone loss and the onset of visceral adiposity. At this time in a woman's life, serum estrogen levels are relatively unaltered, so that the hypothesis that hypoestrogenemia is the sole cause of bone loss and visceral obesity cannot possibly offer a full explanation. An alternative explanation, arising from animal models and human data, is that both physiologic aberrations - obesity and osteoporosis - arise, at least in part from rising FSH levels...
July 31, 2018: Endocrinology
Julie L Youngblood, Tanner F Coleman, Shannon W Davis
The pituitary gland is a critical organ that is necessary for many physiological processes, including growth, reproduction, and stress response. The secretion of pituitary hormones from specific cell types regulates these essential processes. Pituitary hormone cell types arise from a common pool of pituitary progenitors, and mutations that disrupt the formation and differentiation of pituitary progenitors result in hypopituitarism. Canonical WNT signaling through CTNNB1 (β-CATENIN) is known to regulate the formation of the POU1F1 lineage of pituitary cell types...
July 30, 2018: Endocrinology
Máire E Doyle, Jennifer L Fiori, Isabel Gonzalez Mariscal, Qing-Rong Liu, Erin Goodstein, Hyekyung Yang, Yu-Kyong Shin, Sara Santa-Cruz Calvo, Fred E Indig, Josephine M Egan
We and others have reported that taste cells in taste buds express many peptides in common with cells in the gut and islets of Langerhans in the pancreas. Islets and taste bud cells express the hormones glucagon and ghrelin, the same ATP-sensitive potassium channel (KATP) responsible for depolarizing the insulin secreting beta (β) cell during glucose-induced insulin secretion, as well as the propeptide processing enzymes PC1/3 and PC2. Given the common expression of functionally specific proteins in taste buds and islets, it is surprising that no one has investigated whether insulin is synthesized in taste bud cells until now...
July 27, 2018: Endocrinology
Sambit Roy, Divya Gandra, Christina Seger, Anindita Biswas, Vitaly A Kushnir, Norbert Gleicher, T Rajendra Kumar, Aritro Sen
Anti-Müllerian hormone (AMH) produced by ovarian granulosa cells (GCs) plays a crucial role in ovarian function. It is used as a diagnostic and/or prognostic marker of fertility as well as for pathophysiological conditions in women. In this study, we investigated the underlying mechanism for regulation of AMH expression in GCs using primary mouse GCs and a human GC tumor -derived KGN cell line. We find that growth differentiation factor 9 (GDF9) and bone morphogenetic factor 15 (BMP15) together (GDF9+BMP15), but not when tested separately, significantly induce AMH expression, in vitro and in vivo (serum AMH)...
July 27, 2018: Endocrinology
Yuhan Bi, Mengxi Jiang, Weiwei Guo, Xiudong Guan, Meishu Xu, Songrong Ren, Da Yang, Nilesh W Gaikwad, Kyle W Selcer, Wen Xie
Steroid sulfatase (STS), a desulfating enzyme that converts steroid sulfates to hormonally active steroids, plays an important role in the homeostasis of sex hormones. STS is expressed in the adipose tissue of both male and female mice, but the role of STS in the development and function of adipose tissue remains largely unknown. In this report, we first showed that the adipose expression of Sts was induced in the high-fat diet (HFD) and ob/ob models of obesity and type 2 diabetes. Transgenic overexpression of the human STS in the adipose tissue of male mice exacerbated the HFD induced metabolic phenotypes, including increased body weight gain and fat mass, and worsened insulin sensitivity, glucose tolerance and energy expenditure, which were accounted for by adipocyte hypertrophy, increased adipose inflammation, and dysregulation of adipogenesis...
July 27, 2018: Endocrinology
Chad D Foradori, Jessica E Healy, Arthur D Zimmerman, Robert J Kemppainen, Melaney A Jones, Casey C Read, B Douglas White, Kun Don Yi, Laura R Hinds, Anthony F Lacagnina, Alicia M Quihuis, Charles B Breckenridge, Robert J Handa
Atrazine (ATR) is a commonly used pre-emergence/early post-emergence herbicide. Rats gavaged with ATR and its chlorometabolites of desethylatrazine (DEA), or deisopropylatrazine (DIA) respond with a rapid and dose-dependent rise in plasma corticosterone, while the major chlorometabolite, diaminochlorotriazine (DACT), has little to no effect on corticosterone levels. In this study, we investigated the possible site(s) of ATR activation of the hypothalamic-pituitary-adrenal (HPA) axis. ATR treatment had no effect on adrenal weights, but altered adrenal morphology...
July 27, 2018: Endocrinology
Zhong-Min Li, David Hernandez-Moreno, Katharina Maria Main, Niels Erik Skakkebæk, Hannu Kiviranta, Jorma Toppari, Ulla Feldt-Rasmussen, Heqing Shen, Karl-Werner Schramm, Meri De Angelis
In utero exposure to persistent organic pollutants (POPs) can result in thyroid function disorder, leading to concerns about their impact on fetal and neonatal development. The present study was performed to investigate the associations between placental levels of various POPs and thyroid hormones (THs). In a prospective Danish study initially established for assessing congenital cryptorchidism, 58 placenta samples were collected from mothers of boys born with (28) and without (30) cryptorchidism. The concentrations of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), organotin chemicals (OTCs), organochlorine pesticides (OCPs), thyroxine (T4), 3,3',5-triiodothyronine (T3), and 3,3',5'-triiodothyronine (rT3) were measured...
July 27, 2018: Endocrinology
Jessica Lee, Zachary Pappalardo, Deeksha Gambhir Chopra, Thomas G Hennings, Ian Vaughn, Christopher Lan, Justin J Choe, Kenny Ang, Steven Chen, Michelle Arkin, Michael T McManus, Michael S German, Gregory M Ku
Insulin production by the pancreatic beta cell is critical for the glucose homeostasis of the whole organism. While transcription factors required for insulin production are known, the upstream pathways that control insulin production are less clear. To further elucidate this regulatory network, we created a genetic interaction map of insulin production by performing ∼20,000 pairwise RNA interference (RNAi) knockdowns of insulin promoter regulators. Our map correctly predicted known physical complexes in the electron transport chain as well as a role for Spry2 in the unfolded protein response...
July 27, 2018: Endocrinology
Cheng Qin, Jiaheng Li, Ke Tang
The paraventricular nucleus of the hypothalamus (PVH), located in the ventral diencephalon adjacent to the third ventricle, is a highly conserved brain region present in species from zebrafish to humans. The PVH is composed of three main types of neurons, including magnocellular, parvocellular, and long-projecting neurons, which play imperative roles in the regulation of energy balance and various endocrinological activities. In this review, we mainly focus on recent findings about the early development of the hypothalamus and the PVH, the functions of the PVH in the modulation of energy homeostasis and in the hypothalamus-pituitary system, and human diseases associated with the PVH such as obesity, short stature, hypertension, and diabetes insipidus...
July 20, 2018: Endocrinology
Jennifer Taher, Christopher Baker, Danielle Alvares, Laraib Ijaz, Mahmood Hussain, Khosrow Adeli
Fundamental complications of insulin resistance and type 2 diabetes include the development of non-alcoholic fatty liver disease and an atherogenic fasting dyslipidemic profile, primarily due to increases in hepatic very low density lipoprotein (VLDL) production. Recently, central glucagon-like peptide-2 receptor (GLP2R) signalling has been implicated in regulating hepatic insulin sensitivity but its role in hepatic lipid and lipoprotein metabolism is unknown. In the current study, we investigated the role of GLP-2 in regulating hepatic lipid and lipoprotein metabolism in Syrian Golden hamsters, C57BL/6J mice, and Glp2r-/- mice on either a chow or a high fat diet (HFD)...
July 19, 2018: Endocrinology
Thomas G Hennings, Deeksha G Chopra, Elizabeth R DeLeon, Halena R VanDeusen, Hiromi Sesaki, Matthew J Merrins, Gregory M Ku
Mitochondria are dynamic organelles that undergo frequent fission and fusion events. Mitochondrial fission is required for ATP production, the tricarboxylic acid (TCA) cycle, and processes beyond metabolism in a cell-type specific manner. Ex vivo and cell line studies have demonstrated that Drp1, a central regulator of mitochondrial fission, is required for glucose stimulated insulin secretion (GSIS) in pancreatic beta cells. Herein, we set out to interrogate the role of Drp1 in beta cell insulin secretion in vivo...
July 19, 2018: Endocrinology
Wenli Liu, Wulin Aerbajinai, Hongzhen Li, Yueqin Liu, Oksana Gavrilova, Shalini Jain, Griffin P Rodgers
Glucose-stimulated insulin secretion (GSIS) is essential for blood glucose homeostasis and is impaired in type 2 diabetes mellitus. Understanding the regulatory components of GSIS has clinical implications for diabetes treatment. Here we found that olfactomedin 4 (OLFM4) is endogenously expressed in pancreatic islet β cells and further investigated its potential roles in glucose homeostasis and the pathogenesis of type 2 diabetes using mouse models. Olfm4-deficient mice showed significantly improved glucose tolerance and significantly increased insulin levels after glucose challenge compared with wild-type (WT) mice...
July 19, 2018: Endocrinology
Meghan S Vermillion, Rebecca L Ursin, Sarah E Attreed, Sabra L Klein
Estriol (E3) is an endogenous estrogen in females with broad biological activity within diverse tissue types. In the context of certain T cell-mediated autoimmune inflammatory disease, E3 can ameliorate disease severity through immunomodulatory mechanisms that decrease tissue inflammation. Severe disease caused by influenza A virus (IAV) infection is also characterized by aberrant inflammation and immunopathology. How E3 might impact the pathogenesis of IAV infection, however, has not been explored. Gonadally intact female C57BL/6 mice that were treated with exogenous E3 during infection with mouse-adapted 2009 H1N1, had reduced total pulmonary inflammation and improved disease outcomes as compared with females that received no hormone...
July 18, 2018: Endocrinology
Paul Le Tissier, Tatiana Fiordelisio Coll, Patrice Mollard
More than 60 years ago, Geoffrey Harris described his "Neurohumoral theory" in which the regulation of pituitary hormone secretion was a "simple" hierarchal relationship, with the hypothalamus as the controller. In models based on this theory, the electrical activity of hypothalamic neurons determines the release of hypophysiotropic hormones into the portal circulation and the pituitary simply responds with secretion of a pulse of hormone into the bloodstream. The development of methodologies allowing monitoring of the activities of members of the hypothalamic-vascular-pituitary unit is increasingly allowing dissection of the mechanisms generating hypothalamic and pituitary pulses...
July 17, 2018: Endocrinology
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