Clinical implications of growth hormone feedback mechanisms

It is now clear that both long-loop and ultrashort-loop feedback mechanisms may operate to autoregulate GH secretion at both central nervous system and pituitary levels. The key components of this control mechanisms involve GH itself, the GH-dependent peptides, somatomedins, and the two specific hypothalamic hypophysiotropic peptides GHRH and somatostatin. Presently, the intimate mechanism(s) and the respective contributions of the different components as well as the possible interactions between them under physiological or pathological conditions await clarification. However, a major role played by the hypothalamic release of somatostatin is clearly emerging. The awareness of GH autoregulation, and that the amounts of GH used for therapy are at or above the total daily GH production suggest caution in the institution of treatment with GH in children with idiopathic short stature, although resilience of the endogenous GH-secretory machinery would be present in these instances. Ideally, a GH replacement therapy should mimic the physiological secretory pattern of GH.