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

Int J Mol Sci. 2021 Sep 14;22(18):9908. 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.

Keywords: GH; adrenal axis; anxiety; corticosterone; glucocorticoid; hypothalamus; metabolism; neuroendocrinology; paraventricular nucleus; stress.

MeSH terms

  • Animals
  • Anxiety / metabolism
  • Circadian Rhythm / drug effects
  • Corticotropin-Releasing Hormone / metabolism*
  • Energy Metabolism / drug effects
  • Feeding Behavior / drug effects
  • Female
  • Ghrelin / pharmacology
  • Glucose / metabolism
  • Growth Hormone / pharmacology
  • Homeostasis / drug effects
  • Mice
  • Mice, Knockout
  • Neurons / drug effects
  • Neurons / metabolism*
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Receptors, Somatotropin / metabolism*
  • Stress, Physiological / drug effects

Substances

  • Ghrelin
  • Receptors, Somatotropin
  • Growth Hormone
  • Corticotropin-Releasing Hormone
  • Glucose