Neuroendocrine control of pulsatile growth hormone release in the human: relationship with gender

Gender has multiple significant influences on the human GH axis in the premenopausal age group (Table 1), and attenuates by approximately 50% the negative impact of age on daily GH secretion rates, the inverse association between total adiposity and GH production, and the positive effect of increased physical fitness on GH secretion. The sex differences in GH axis activity are highly specific mechanistically, and namely entail the mass of GH secreted per burst (greater in women than men), and the orderliness of the 24-hour GH release process (less orderly pattern in women). Moreover, physiological regulation of the GH-IGF-I axis is evident within the follicular phase of the normal human menstrual cycle, wherein mean serum GH and plasma IGF-I concentrations rise concurrently with increased oestradiol secretion in the preovulatory phase. Oestrogen, directly or indirectly (e.g. via long-term changes in visceral and subcutaneous fat distribution), serves as the proximate mediator of many gender differences, and probably mediates most of the acute sex-steroid effects of both testosterone and oestradiol on the human GH-IGF-I axis. In conclusion, oestrogen regulates the physiological output of the GH-IGF-I axis both quantitatively (daily GH secretion rate) and qualitatively (organization or orderliness of GH release). The actions of oestrogen are probably achieved via alterations in GHRH and somatostatin activities and their reciprocal interactions. Current evidence concerning the role of oestrogen favours an increase in somatotroph responsiveness to GHRH, with or without decreased effects of somatostatin. Whether putative GHRPs, galanin, etc., participate in the potent amplifying actions of oestrogen on the GH axis is not known. Thus, gender and sex steroids are potent pathophysiological regulators of the orderliness and pulsatile mass of GH secreted in humans.