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Johannes D. Veldhuis, Kristi L. Mielke, Mihaela Cosma, Cacia Soares-Welch, Remberto Paulo, John M. Miles, Cyril Y. Bowers, 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, The Journal of Clinical Endocrinology & Metabolism, Volume 94, Issue 3, 1 March 2009, Pages 973–981, https://doi.org/10.1210/jc.2008-2108
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Abstract
Background: How endogenous testosterone (Te), 5α-dihydrotestosterone (DHT), and estradiol (E2) regulate pulsatile GH secretion is not understood.
Hypothesis: Conversion of Te to androgenic (Te→DHT) or estrogenic (Te→E2) products directs GH secretion.
Subjects and Location: Healthy older men (N = 42, ages 50–79 yr) participated at an academic medical center.
Methods: We inhibited 5α-reduction with dutasteride and aromatization with anastrozole during a pharmacological Te clamp and infused somatostatin (SS), GHRH, GH-releasing peptide-2 (GHRP-2), 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 E2 concentrations by 1.9-fold above placebo/placebo. Te/dutasteride and Te/anastrozole reduced stimulated DHT and E2 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 E2 jointly predict GH responses to the triple stimulus (positively for Te, P = 0.006, and negatively for E2, 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 E2 along with abdominal visceral fat determine the selective actions of GH secretagogues and SS.