Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo 05508-000, SP, Brazil.
Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA.
Int J Mol Sci. 2021 Sep 14;22(18):9908. doi: 10.3390/ijms22189908.
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.
促肾上腺皮质激素释放激素(CRH)细胞是对下丘脑室旁核(PVH)中生长激素(GH)反应的主要神经元群体。然而,GH 受体(GHR)信号在 CRH 神经元中的生理重要性目前尚不清楚。因此,本研究的主要目的是研究 GHR 敲除对雄性和雌性小鼠 CRH 表达细胞的影响。CRH 细胞中的 GHR 敲除不会导致体重、体成分、食物摄入、底物氧化、运动活性、葡萄糖耐量、胰岛素敏感性、2-脱氧-D-葡萄糖的代偿性反应和胃饥饿素诱导的食物摄入发生显著变化。然而,在携带 CRH 细胞中 GHR 敲除的雌性小鼠中观察到能量消耗减少。CRH 细胞中 GHR 的缺失不会影响雄性和雌性小鼠的焦虑、昼夜皮质酮水平或束缚应激诱导的皮质酮分泌和 PVH 神经元的激活。总之,CRH 表达神经元中的 GHR 敲除不会导致代谢、下丘脑-垂体-肾上腺轴、急性应激反应或焦虑在小鼠中发生重大改变。考虑到之前的研究表明,中枢 GHR 信号在代谢应激情况下调节体内平衡,未来的研究仍需要确定 GH 对 CRH 神经元的作用的潜在生理重要性。