Central Regulation of Metabolism by Growth Hormone

Abstract

Growth hormone (GH) is secreted by the pituitary gland, and in addition to its classical functions of regulating height, protein synthesis, tissue growth, and cell proliferation, GH exerts profound effects on metabolism. In this regard, GH stimulates lipolysis in white adipose tissue and antagonizes insulin's effects on glycemic control. During the last decade, a wide distribution of GH-responsive neurons were identified in numerous brain areas, especially in hypothalamic nuclei, that control metabolism. The specific role of GH action in different neuronal populations is now starting to be uncovered, and so far, it indicates that the brain is an important target of GH for the regulation of food intake, energy expenditure, and glycemia and neuroendocrine changes, particularly in response to different forms of metabolic stress such as glucoprivation, food restriction, and physical exercise. The objective of the present review is to summarize the current knowledge about the potential role of GH action in the brain for the regulation of different metabolic aspects. The findings gathered here allow us to suggest that GH represents a hormonal factor that conveys homeostatic information to the brain to produce metabolic adjustments in order to promote energy homeostasis.

Keywords: GH; cytokines; energy balance; glucose homeostasis; hypothalamus.

Figure 1

Neuroendocrine factors that control the pulsatile secretion of growth hormone (GH). Ghrelin and GH-releasing hormone (GHRH) stimulate pituitary GH secretion, whereas somatostatin (SST) inhibits it. The example of the pulsatile secretion of GH was obtained from a C57BL/6 eight-week-old male mouse after 36 serial blood collections in a 10-min interval (lights on at 7 am; 12-h light/dark cycle). Note that GH has central and peripheral actions (e.g., on the liver, muscle and white adipose tissue), in which the stimulation of insulin-like growth factor 1 (IGF-1) secretion from the liver plays a major role controlling somatic growth.

Figure 2

GH-responsive neurons are found in several brain structures, and GH receptor signaling regulates different neurological aspects. Coronal photomicrographs of different parts of the mouse brain showing immunoreactivity against the phosphorylation of the signal transducer and activator of transcription 5 after an acute GH injection. Previous studies indicated that GH receptor signaling in different brain areas regulates distinct physiological parameters. Although GH-responsive neurons are abundantly found in the paraventricular nucleus of the hypothalamus, the exact role played by GH in these cells is still unknown.

Figure 3

Neurochemical phenotype of GH-responsive neurons in the hypothalamic arcuate and paraventricular nuclei. (A) Scheme illustrating the approximate percentage of responsiveness to GH in arcuate nucleus neurons that express agouti-related peptide (AgRP), proopiomelanocortin (POMC), choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), GH-releasing hormone (GHRH) and kisspeptins (Kp). (B) Scheme illustrating the approximate percentage of responsiveness to GH in hypothalamic paraventricular nucleus neurons that express somatostatin (SST), TH, corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), oxytocin (OXT) and vasopressin (AVP). The relative size of circles and ellipsoids indicates the approximate percentage of neurons in these nuclei which are responsive to GH.