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Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-1388
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The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 3 944-950
Copyright © 2008 by The Endocrine Society

Gonadal Status and Body Mass Index Jointly Determine Growth Hormone (GH)-Releasing Hormone/GH-Releasing Peptide Synergy in Healthy Men

Remberto C. Paulo, Mihaela Cosma, Cacia Soares-Welch, Joy N. Bailey, Kristi L. Mielke, John M. Miles, Cyril Y. Bowers and Johannes D. Veldhuis

Departments of Pediatrics (R.C.P.) and Internal Medicine (M.C., C.S.-W., J.N.B., K.L.M., J.M.M., J.D.V.), Endocrine Research Unit, Clinical Translational Research Center, Mayo Medical and Graduate Schools, Mayo Clinic, Rochester, Minnesota 55901; and Division of Endocrinology (C.Y.B.), Department of Internal Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana 70112

Address all correspondence and requests for reprints to: Johannes D. Veldhuis, Departments of Pediatrics and Internal Medicine, Endocrine Research Unit, Clinical Translational Research Center, Mayo Medical and Graduate Schools, Mayo Clinic, Rochester, Minnesota 55901. E-mail: Veldhuis.Johannes{at}mayo.edu.

Context: Sex steroid hormones potentiate whereas increased body mass index (BMI) represses GH secretion. Whether sex steroids modify the negative effect of BMI on secretagogue-induced GH secretion in men is not known. The issue is important in designing GH-stimulation regimens that are relatively insensitive to both gonadal status and adiposity.

Objective: Our objective was to compare the relationships between BMI and peptide-stimulated GH secretion in men with normal and reduced testosterone and estradiol availability.

Setting: The study was performed at an academic medical center.

Subjects: Healthy young men were included in the study.

Interventions: Randomized separate-day iv infusion of saline and/or maximally effective doses of L-arginine/GHRH, L-arginine/GH-releasing peptide (GHRP)-2, and GHRH/GHRP-2 in eugonadal (n = 12) and experimentally hypogonadal (n = 10) men was performed.

Outcomes: Regression of paired secretagogue-induced GH responses on BMI was determined.

Results: In eugonadal men, peak GH concentrations correlated negatively with BMI. In particular, BMI accounted for only 38% of the response variability after L-arginine/GHRH (P = 0.0165), but 62% after GHRH/GHRP-2 (P = 0.0012) and 65% after L-arginine/GHRP-2 (P = 0.00075). In contrast, in hypogonadal men, GH responses were uncorrelated with BMI. The negative effects of BMI on peak GH responses in eugonadal and hypogonadal states differed most markedly after stimulation with GHRH/GHRP-2 (P = 0.0019). This contrast was corroborated using integrated GH responses (P = 0.0007).

Conclusions: Short-term experimental gonadal sex hormone depletion attenuates dual secretagogue-stimulated GH secretion in lean young men. The inhibitory effect of relative adiposity on GH secretion appears to predominate over that of acute sex steroid withdrawal.







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