Effects of Growth Hormone Receptor Ablation in Corticotropin-Releasing Hormone Cells.

Willian O Dos Santos,Daniela O Gusmao,Edward O List,Jose Donato,Frederick Wasinski,John J Kopchick

doi:10.3390/ijms22189908

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.

Highlights

Growth hormone (GH) is secreted by the pituitary gland and stimulates protein synthesis and cell proliferation, as well as tissue and body growth [1,2,3]
Distribution of Corticotropin-releasing hormone (CRH) Neurons That Are Responsive to GH
We observed some CRH neurons that were responsive to GH in the anterior division of the bed nucleus of the stria terminalis (BNST) (Figure 1a) and in the lateral hypothalamic area (LHA) (Figure 1b)

Summary

Introduction

Growth hormone (GH) is secreted by the pituitary gland and stimulates protein synthesis and cell proliferation, as well as tissue and body growth [1,2,3]. The importance of GH secretion during situations of metabolic stress is not completely understood, but it may be associated with GH action promoting physiological adjustments in order to restore homeostasis [13] In accordance with this idea, GH or GH receptor (GHR) deficiency increases the risk of hypoglycemia [14,15]. A previous study has shown that GHR signaling is able to regulate food intake, body adiposity and insulin sensitivity in late pregnant mice [23] Taken together, these studies show that GH secretion during situations of metabolic stress or higher energy requirements is necessary to produce appropriate physiological adjustments that help to cope with changes in homeostasis

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