Understanding the multifactorial control of growth hormone release by somatotropes: lessons from comparative...

Control of postnatal growth is the main, but not the only, role for growth hormone (GH) as this hormone also contributes to regulating metabolism, reproduction, immunity, development, and osmoregulation in different species. Likely owing to this variety of group-specific functions, GH production is differentially regulated across vertebrates, with an apparent evolutionary trend to simplification, especially in the number of stimulatory factors governing substantially GH release. Thus, teleosts exhibit a multifactorial regulation of GH secretion, with a number of factors, from the newly discovered fish GH-releasing hormone (GHRH) to pituitary adenylate cyclase-activating peptide (PACAP) but also gonadotropin-releasing hormone, dopamine, corticotropin-releasing hormone, and somatostatin(s) directly controlling somatotropes. In amphibians and reptiles, GH secretion is primarily stimulated by the major hypothalamic peptides GHRH and PACAP and inhibited by somatostatin(s), while other factors (ghrelin, thyrotropin-releasing hormone) also influence GH release. Finally, in birds and mammals, primary control of GH secretion is exerted by a dual interplay between GHRH and somatostatin. In addition, somatotrope function is modulated by additional hypothalamic and peripheral factors (e.g., ghrelin, leptin, insulin-like growth factor-I), which together enable a balanced integration of feedback signals related to processes in which GH plays a relevant regulatory role, such as metabolic and energy status, reproductive, and immune function. Interestingly, in contrast to the high number of stimulatory factors impinging upon somatotropes, somatostatin(s) stand(s) as the main primary inhibitory regulator(s) for this cell type.