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

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

Research output: Contribution to journalArticle

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)973-981
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume94
Issue number3
DOIs
StatePublished - Mar 2009

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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