In vivo semiquantification of hypothalamic growth hormone-releasing hormone (GHRH) output in humans: Evidence for relative GHRH deficiency in aging

GH secretion declines with aging. The neuroendocrine mechanisms of somatopa use are uncertain. To semiquantify endogenous hypothalamic GHRH output, we measured the suppressibility of spontaneous and GHRH-stimulated GH secretio n by graded doses of a specific competitive GHRH receptor antagonist (N-Ac- Tyr(1),D-Arg(2))GHRH-(1-29) in healthy young and elderly men. Nocturnal GH was about 30% lower in the elderly than in the young. Graded boluses of GHR H elicited dose-dependent GH responses, with no difference between the two age groups. Graded infusions of GHRH antagonist suppressed GH responses to GHRH in a dose-dependent manner, but with similar potency in both groups. T he degree of inhibition depended on the magnitude of GHRH bolus: the dose-i nhibition curves for the low GHRH boluses were shifted to the left compared to those with the high GHRH bolus (P = 0.01). Similarly, the dose-inhibiti on curve for spontaneous GH secretion was shifted to the left for the elder ly compared to the young men (P = 0.01). Thus, the model of graded infusion s of GHRH antagonist differentiates between different amounts of GHRH prese nted to the pituitary, permitting semiquantification of the endogenous hypo thalamic GHRH output in vivo. Our data suggest that there is an age-depende nt decrease in the endogenous hypothalamic GHRH output contributing to the age-associated GH decline.