Semiquantification of hypothalamic GH-releasing hormone output in women: Evidence for sexual dimorphism in the mechanism of the somatopause

The neuroendocrine mechanisms underlying the decline of GH with aging (soma topause) are uncertain. We recently found that the age-dependent diminution of the hypothalamic GH-releasing hormone (GHRH) output contributes to the somatopause in men. As the regulatory mechanisms of GH secretion are sexual ly dimorphic, we assessed the suppressibility of spontaneous and GHRH-stimu lated GH I secretion by graded doses of a specific competitive GHRH recepto r antagonist in nine young (20-27 yr old) and eight elderly (65-77 yr old) healthy nonobese women to semiquantify hypothalamic GHRH output. Nocturnal mean GH was lower in elderly women (2.2 +/- 0.4 vs. 0.9 +/- 0.2 mug/liter; P = 0.01). Graded boluses of GHRH-44 resulted in similar GH responses in bo th populations (P = 0.28). Graded infusions of GHRH antagonist inhibited in a dose-dependent manner the GH responses to GHRH in both groups (P = 0.000 1-0.04). The dose-inhibition curve for the lowest GHRH bolus dose was shift ed to the left compared with the highest one (P = 0.04). However, the dose- inhibition curves for spontaneous GH secretion were not different in young and elderly women (P = 0.50). Thus, the female somatopause is not associate d with a measurable decrease in hypothalamic GHRH output. When the dose-inh ibition curves for young men and young women were compared, the latter was shifted to the left (P = 0.009), suggesting that the somatotropic,system in women operates with less GHRH. We conclude that the contribution of endoge nous GHRH to the maintenance of GH secretion and the neuroendocrine mechani sms of somatopause in humans are sexually dimorphic.