Secretagogue type, sex-steroid milieu, and abdominal visceral adiposity individually determine secretagogue-stimulated cortisol secretion

Design: While androgens and estrogens control glucocorticoid secretion in animal models, how the sex-steroid milieu determines cortisol secretion in humans is less clear. To address this issue, cortisol was measured in archival sera obtained at 10-min intervals for 5 h in 42 healthy men administered double placebo, placebo and testosterone, testosterone and dutasteride (to block 5α-reductases type I and type II), or testosterone and anastrozole (to block aromatase) in a double-blind, placebocontrolled, prospectively randomized design. Methods: Subjects received i.v. injection of saline, GHRH, GH-releasing peptide-2 (GHRP-2), somatostatin (SS), and GHRP-2/GHRH/L-arginine (triple stimulus) each on separate mornings fasting. Outcomes comprised cortisol concentrations, pulsatile cortisol secretion, and relationships with age or abdominal visceral fat (AVF). Results: By ANCOVA, baseline (saline-infused) cortisol concentrations (nmol/l) did not differ among the sex-steroid milieus (overall mean 364±14). In contrast, stimulated peak cortisol concentrations were strongly determined by secretagogue type (P<0.001) as follows: triple stimulus (868<27)OGHRP-2 (616<42)Osaline=SS=GHRH (grand mean 420±21). After GHRP-2 injection, pulsatile cortisol secretion increased with age (R²=0.16, P=0.012). After the triple stimulus, pulsatile cortisol secretion correlated i) inversely with serum 5α-dihydrotestosterone (DHT) concentrations (R²=0.53, P=0.026) and ii) directly with computerized tomography-estimated AVF (R2Z0.11, PZ0.038). Conclusion: Age, DHT concentrations, AVF, and secretagogue type influence pulsatile cortisol secretion at least in men. Further studies should be performed to assess ACTH secretion and native ghrelin action in defined sex-steroid milieus.