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The Endocrine Response to Ghrelin as a Function of Gender in Humans in Young and Elderly Subjects

Division of Endocrinology and Metabolism, Department of Internal Medicine (F.B., A.B., C.Go., F.P., S.D., C.Ga., R.D., E.A., E.G.), and Division of Geriatrics, Department of Medical and Surgical Disclipines (C.C., M.B.), University of Turin, 10126 Turin, Italy; and Division of Endocrinology and Metabolism, Department of Internal Medicine (A.J.v.d.L.), Erasmus University of Rotterdam, 3015 Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: E. Ghigo, M.D., Department of Internal Medicine, Division of Endocrinology, University of Turin, Corso Dogliotti 14, 10126 Torino, Italy. E-mail: ezio. ghigo{at}unito.it.

Ghrelin modulates somatotroph, lactotroph, corticotroph, and insulin secretion and glucose metabolism. To clarify the influence of gender and age on the endocrine actions of ghrelin in humans, we studied the effects of ghrelin (1.0 µg/kg iv) or placebo on GH, prolactin (PRL), ACTH, cortisol, insulin, glucagon, and glucose levels in 18 young subjects (YS) and 16 elderly subjects (ES) of both genders. The GH response to GHRH (1.0 µg/kg iv) was also studied. The GH response to ghrelin in YS was higher (P < 0.01) than in ES and both higher (P < 0.01) than to GHRH, without gender-related differences. In YS ghrelin also induced: 1) gender-independent increase (P < 0.01) in PRL, ACTH, and cortisol levels; 2) gender-independent increase in glucose levels (P < 0.01); 3) decrease (P < 0.01) in insulin levels in male YS; and 4) no change in glucagon. In ES, ghrelin induced gender-independent PRL, ACTH, and cortisol responses (P < 0.01). In ES ghrelin elicited gender-independent transient decrease in insulin (P < 0.01) coupled with increase in glucose levels (P < 0.05). In conclusion, the GH-releasing effect of ghrelin is independent of gender but undergoes age-related decrease. The effect of ghrelin on lactotroph and corticotroph secretion is age and gender independent. In both ES and YS, ghrelin influences insulin secretion and glucose metabolism.

This work was supported by Eureka (Peptido project 1923), University of Turin, Studio Malattie Endocrino Metaboliche Foundation, and Europeptides.

Abbreviations: ES, Elderly subjects; GHS, GH secretagogue; GHS-R, GHS-specific receptor; IRMA, immunoradiometric assay; PRL, prolactin; YS, young subjects.

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