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 5alpha-reductases type I and type II), or testosterone and anastrozole (to block aromatase) in a double-blind, placebo-controlled, 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)>GHRP-2 (616+/-42)>saline=SS=GHRH (grand mean 420+/-21). After GHRP-2 injection, pulsatile cortisol secretion increased with age (R(2)=0.16, P=0.012). After the triple stimulus, pulsatile cortisol secretion correlated i) inversely with serum 5alpha-dihydrotestosterone (DHT) concentrations (R(2)=0.53, P=0.026) and ii) directly with computerized tomography-estimated AVF (R(2)=0.11, P=0.038).

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.