METYRAPONE INDUCED INCREASE IN PLASMA CORTICOTROPIN IS NOT ASSOCIATED WITH CHANGES IN PERIPHERAL VENOUS ARGININE-VASOPRESSIN OR CORTICOTROPIN-RELEASING FACTOR

The responses of the ''stress hormones'' cortisol, 11-deoxycortisol, ACTH, vasopressin (AVP), and corticotropin releasing factor (CRF) were studied in 6 normal males in response to acute cortisol deficiency induced by the 11-beta-hydroxylase inhibitor, metyrapone. A 750 mg dose was administered orally at 08:00 h on day 1 and at 4 hourly intervals over a 24-h period. A 20 mg tablet of hydrocortisone or placebo was then given at 08:00 h on day 2, according to a randomized crossover design. Each subject was restudied after an interval of at least one month. Blood samples were taken for all hormones at 08:00 h on day 1 and at 04:00 h on day 2. Thereafter ACTH and AVP were sampled at 1O-min intervals, CRF at 20-min intervals, and cortisol and 11-deoxycortisol at hourly intervals until 12:00 h on day 2. Cortisol (mean+/-SE) fell from 628+/-218 nmol/l at 08:00 h (day 1) to a minimum of 230+/-78 nmol/l at 05:00 h on day 2. Plasma 11-deoxycortisol rose from 14.0+/-0.8 nmol/l to a maximum of 622+/-36 nmol/l and plasma ACTH rose from 8.71+/-1.64 pmol/l to a maximum of 166.2+/-57.5 pmol/l. Diurnal rhythmicity of plasma ACTH was maintained. There was no detectable change in plasma levels of AVP or CRF from baseline (AVP 2.5+/-0.8 pmol/l, CRF 3.4+/-0.5 pmol/l). Four h following the administration of hydrocortisone, mean plasma ACTH (37.3+/-16.8 pmol/l) and 11-deoxycortisol (248+/-110 nmol/l) had fallen, although the difference between placebo and control groups failed to reach significance. There was no detectable suppression of peripheral plasma levels of AVP or CRF. Acute blockade of cortisol synthesis, therefore results in a large increase in plasma ACTH which is unaccompanied by a detectable rise in peripheral plasma levels of AVP or CRF. This suggests that decreased cortisol feedback increases the ''gain'' of AVP and CRF on pituitary ACTH release, or that factor(s) other than AVP or CRF may modulate ACTH release.