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This version published online on December 11, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-1388
A more recent version of this article appeared on March 1, 2008
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Submitted on June 22, 2007
Accepted on December 4, 2007

Gonadal Status and Body-Mass Index Jointly Determine GHRH/GHRP Synergy in Healthy Men

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

Departments of Pediatrics and Internal Medicine, Endocrine Research Unit, Clinical Translational Research Center, Mayo Medical and Graduate Schools, Mayo Clinic, Rochester MN 55901; Division of Endocrinology, Department of Internal Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112

* To whom correspondence should be addressed. 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.

Objectives. To compare the relationships between BMI and peptide-stimulated GH secretion in men with normal and reduced Te and E2 availability.

Setting. Academic medical center.

Subjects. Healthy young men.

Interventions. Randomized separate-day iv infusions of saline and/or maximally effective doses of L-arginine/GHRH, L-arginine/GHRP-2, and GHRH/GHRP-2 in eugonadal (N = 12) and experimentally hypogonadal (N = 10) men.

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

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 eu- 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).

Conclusion. 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.
Key words: somatotrope • testosterone • human • estradiol • GHRH • GHRP • ghrelin • somatostatin






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