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Effects of Growth Hormone Receptor Ablation in Corticotropin-Releasing Hormone Cells
Authors:Willian O dos Santos  Daniela O Gusmao  Frederick Wasinski  Edward O List  John J Kopchick  Jose Donato  Jr
Affiliation:1.Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo 05508-000, SP, Brazil; (W.O.d.S.); (D.O.G.); (F.W.);2.Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA; (E.O.L.); (J.J.K.)
Abstract:Corticotropin-releasing hormone (CRH) cells are the dominant neuronal population responsive to the growth hormone (GH) in the paraventricular nucleus of the hypothalamus (PVH). However, the physiological importance of GH receptor (GHR) signaling in CRH neurons is currently unknown. Thus, the main objective of the present study was to investigate the consequences of GHR ablation in CRH-expressing cells of male and female mice. GHR ablation in CRH cells did not cause significant changes in body weight, body composition, food intake, substrate oxidation, locomotor activity, glucose tolerance, insulin sensitivity, counterregulatory response to 2-deoxy-D-glucose and ghrelin-induced food intake. However, reduced energy expenditure was observed in female mice carrying GHR ablation in CRH cells. The absence of GHR in CRH cells did not affect anxiety, circadian glucocorticoid levels or restraint-stress-induced corticosterone secretion and activation of PVH neurons in both male and female mice. In summary, GHR ablation, specifically in CRH-expressing neurons, does not lead to major alterations in metabolism, hypothalamic–pituitary–adrenal axis, acute stress response or anxiety in mice. Considering the previous studies showing that central GHR signaling regulates homeostasis in situations of metabolic stress, future studies are still necessary to identify the potential physiological importance of GH action on CRH neurons.
Keywords:adrenal axis  anxiety  corticosterone  GH  glucocorticoid  hypothalamus  metabolism  neuroendocrinology  paraventricular nucleus  stress
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