Negative feedback loops and hormonal factors that regulate growth hormone secretion.

Growth hormone (GH) acts as a master regulator of body growth in addition to playing a crucial role in various physiological processes. GH is produced by somatotropic cells in the anterior pituitary gland, and its levels in the blood display a pulsatile pattern. Secretion of GH is primarily regulated by hypothalamic factors released into the hypophyseal portal system. The regulation of GH release involves multiple negative feedback mechanisms that detect changes in circulating levels of either GH or insulin-like growth factor 1 (IGF-1). These regulatory loops occur at both the pituitary and hypothalamic levels, indicating the presence of redundant control mechanisms. Furthermore, GH is secreted in high amounts during specific situations, including the neonatal period, pregnancy, hypoglycemia, and prolonged food deprivation. Numerous studies published in recent years have revealed new insights into the mechanisms regulating pulsatile GH secretion, including the importance of negative feedback loops, hormonal factors (e.g., GH secretagogue receptor and glucagon-like peptide-1 receptor ligands, insulin, and sex steroids), and specific neuronal circuits. Therefore, the objective of this review is to summarize and discuss these novel findings and their implications for understanding the neuroendocrine control of GH secretion.