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Semiquantification of Hypothalamic GH-Releasing Hormone Output in Women: Evidence for Sexual Dimorphism in the Mechanism of the Somatopause

Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Michigan Medical Center (J.J.O., M.R.-A., A.L.B.), and Department of Veterans Affairs Medical Center (R.D.-F., A.L.B.), Ann Arbor, Michigan 48109

Address all correspondence and requests for reprints to: Ariel L. Barkan, M.D., Division of Endocrinology and Metabolism, 3920 Taubman Center, Room 0354, University of Michigan Medical Center, Ann Arbor, Michigan 48109. E-mail: abarkan{at}umich.edu

Abstract

The neuroendocrine mechanisms underlying the decline of GH with aging (somatopause) 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 sexually dimorphic, we assessed the suppressibility of spontaneous and GHRH-stimulated GH secretion by graded doses of a specific competitive GHRH receptor 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 µg/liter; P = 0.01). Graded boluses of GHRH-44 resulted in similar GH responses in both populations (P = 0.28). Graded infusions of GHRH antagonist inhibited in a dose-dependent manner the GH responses to GHRH in both groups (P = 0.0001–0.04). The dose-inhibition curve for the lowest GHRH bolus dose was shifted 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 associated with a measurable decrease in hypothalamic GHRH output. When the dose-inhibition 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 endogenous GHRH to the maintenance of GH secretion and the neuroendocrine mechanisms of somatopause in humans are sexually dimorphic.

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