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Short-Term Testosterone Supplementation Relieves Growth Hormone Autonegative Feedback in Men

Division of Endocrinology and Metabolism (J.D.V.), Department of Internal Medicine, Mayo Medical and Graduate Schools of Medicine, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905; Division of Endocrinology (W.S.E., A.L.W.), Department of Internal Medicine, Department of Obstetrics and Gynecology (W.S.E.), General Clinical Research Center, and Department of Human Services (A.L.W.), School of Education, General Clinical Research Center, University of Virginia Health System, Charlottesville, Virginia 22908; Research and Development Office (A.I.), Salem Veterans Affairs Medical Center, Salem, Virginia 24153; and Department of Internal Medicine (C.Y.B.), Division of Endocrinology and Metabolism, Tulane Medical School, New Orleans, Louisiana 70112-2699

Address all correspondence and requests for reprints to: Johannes D. Veldhuis, Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Medical and Graduate Schools of Medicine, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905. E-mail: veldhuis.johannes{at}mayo.edu.

The present study tests the postulate that testosterone (Te) stimulates GH secretion, in part, by attenuating autonegative feedback. To this end, 13 healthy men (ages 43–71 yr) received three consecutive weekly im injections of placebo (Pl) (n = 7) or Te (200 mg) (n = 6) in a prospectively randomized, double-blind, parallel-cohort design. An iv pulse of saline or recombinant human (rh)GH (3 µg/kg·6 min) was infused 2 h before bolus saline or GH-releasing peptide (GHRP)-2 (1 µg/kg) in the fasting state. Blood was withdrawn every 10 min, GH concentrations were quantitated by chemiluminometry, secretion was determined by deconvolution analysis, and outcomes were compared by ANOVA. After Pl, rhGH suppressed basal, pulsatile, and GHRP-2-stimulated GH secretion by 2.6-, 2.4-, and 2.1-fold, respectively (each P < 0.03), and truncated GHRP-2-stimulated GH secretory bursts (P < 0.005). Compared with Pl, Te: 1) stimulated basal and pulsatile GH secretion by 1.9 and 2.4-fold (P < 0.01 and P < 0.02), respectively; 2) reduced feedback on basal GH secretion (P < 0.01); 3) blunted GHRP-2-stimulation by 1.9-fold (P < 0.01); and 4) facilitated initial recovery of rhGH-suppressed GH concentrations (P < 0.005). The foregoing actions were selective, inasmuch as Te did not relieve autoinhibition of pulsatile GH secretion.

In summary, short-term Te supplementation decreases rhGH-imposed negative feedback on basal GH secretion and enhances early escape of GH from autoinhibition. In principle, such actions could potentiate the renewal of high-amplitude pulses of GH in androgen-replete individuals.

This work was supported, in part, by MO1 RR00847 and RR00585 (to the GCRCs of the University of Virginia and Mayo Clinic) from the National Center for Research Resources (Rockville, MD), and R01 AG-19695 (to J.D.V.) from the National Institutes of Health (Bethesda, MD).

Abbreviations: CV, Coefficient of variation; GCRC, General Clinical Research Center; GHRP, GH-releasing peptide; Pl, placebo; rh, recombinant human; Te, testosterone.

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