Recovery of responses to ovine corticotropin-releasing hormone after withdrawal of a short course of glucocorticoid.
To characterize the recovery of the hypothalamic-pituitary-adrenal axis from suppression by short-term glucocorticoid treatment, we examined the responses to ovine CRH (oCRH) before and after prednisolone administration. Eight normal male volunteers were studied before (control) and after administration of 25 mg prednisolone twice daily orally for 14 days. Data are mean +/- SEM. The ACTH basal level was suppressed 24 h after prednisolone withdrawal (1.7 +/- 0.4 pmol/L vs. control, 3.5 +/- 0.6, P less than 0.02), but the ACTH response to oCRH was not significantly different from control (peak 12.8 +/- 2.0 pmol/L vs. 13.5 +/- 12.1, respectively). Seventy-two h post prednisolone basal ACTH levels had recovered to pretreatment values. Cortisol levels, both basal and in response to oCRH, were significantly suppressed 24 h post prednisolone (P less than 0.001). By 72 h post prednisolone, both basal and oCRH-stimulated cortisol had recovered to pretreatment levels. Dehydroepiandrosterone (DHEA), both basal and stimulated, was significantly suppressed 24 h post prednisolone (P less than 0.001). In contrast to cortisol, basal and peak DHEA remained suppressed 72 h post prednisolone (basal DHEA 9.1 +/- 1.1 nmol/L, P less than 0.05 vs. control; peak DHEA 20.0 +/- 3.3 nmol/L, P less than 0.01 vs. control). When expressed as percent rise, however, the DHEA response to oCRH was not significantly different from control. DHEA sulfate (DHEAS) was significantly lower than control at both 24 and 72 h post prednisolone (1.8 +/- 0.3 and 3.3 +/- 0.4 mumol/L respectively; control 7.2 +/- 0.7 mumol/L; P less than 0.001). The ratio of basal DHEA to DHEAS was significantly higher than control 72 h post prednisolone, indicating that DHEAS was more profoundly suppressed than DHEA. We conclude that after a short course of prednisolone pituitary ACTH secretion is the first parameter of the hypothalamic-pituitary-adrenal axis to recover. Hypothalamic secretion of CRH recovers next, followed by recovery of cortisol secretion. Secretion of DHEA and DHEAS remain suppressed after recovery of cortisol. This suppression may be caused by inhibition of sulfokinase activity by glucocorticoid.
Brigell
D F
DF
Department of Medicine, University of Chicago, Pritzker School of Medicine, Illinois 60637-1470.
Fang
V S
VS
Rosenfield
R L
RL
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D011239:Prednisolone / Q000494:pharmacology*
D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D011239:Prednisolone; D006854:Hydrocortisone