Aromatase and 5α-Reductase Inhibition during an Exogenous Testosterone Clamp Unveils Selective Sex Steroid Modulation of Somatostatin and Growth Hormone Secretagogue Actions in Healthy Older Men

Background: How endogenous testosterone (Te), 5 alpha-dihydrotestosterone (DHT), and estradiol (E-2) regulate pulsatile GH secretion is not understood. Hypothesis: Conversion of Te to androgenic (Te -> DHT) or estrogenic (Te -> E-2) products directs GH secretion. Subjects and Location: Healthy older men (N = 42, ages 50-79 yr) participated at an academic medical center. Methods: Weinhibited 5 alpha-reduction with dutasteride and aromatization with anastrozole during a pharmacological Te clamp and infused somatostatin (SS), GHRH, GH-releasing peptide-2 (GHRP2), and L-arginine/GHRH/GHRP-2 (triple stimulus) to modulate GH secretion. Endpoints: Deconvolution-estimated basal and pulsatile GH secretion was assessed. Results: Administration of Te/placebo elevated Te by 2.8-fold, DHT by 2.6-fold, and E-2 concentrations by 1.9-fold above placebo/ placebo. Te/dutasteride and Te/anastrozole reduced stimulated DHT and E-2 by 89 and 86%, respectively. Stepwise forward-selection regression analysis revealed that 1) Te positively determines mean (P = 0.017) and peak (P < 0.001) GH concentrations, basal GH secretion (P = 0.015), and pulsatile GH secretion stimulated by GHRP-2 (P < 0.001); 2) Te and E-2 jointly predict GH responses to the triple stimulus (positively for Te, P = 0.006, and negatively for E-2, P = 0.031); and 3) DHT correlates positively with pulsatile GH secretion during SS infusion (P = 0.011). These effects persisted when abdominal visceral fat was included in the regression. Conclusion: The present outcomes suggest a tetrapartite model of GH regulation in men, in which systemic concentrations of Te, DHT, and E-2 along with abdominal visceral fat determine the selective actions of GH secretagogues and SS. (J Clin Endocrinol Metab 94: 973-981, 2009)