우울병 환자에서 부신피 질자극호르몬 유리인자로 유발한 글루코코르티코이드 급속되먹임 효과

Glucocorticoid Fast-feedback Inhibition after Corticotropin Releasing Factor Stimulation in Depressed Patients

The regulation of limbic-hypothalamic-pituitary-adrenal(LHPA) axis involves both a delayed feedback system as well as a less well studied “fast-feedback” (FFB) system. Glucocorticoid FFB inhibition of adrenocorticotropic hormone(ACTH) may be of importance in the acute control of the LHPA axis in man, and probably has a modulatory effect on the response to stress which limits the secretory response when two stresses occur in rapid succession. This study aims to demonstrate FFB with ovine coticotropin-releasing factor(oCRF) administration, and to determine the possible site(s) on which glucocorticoid exerts its FFB inhibition of ACTH secretion in normal humans. A third objective is to document the importance of pituitary- mediated FFB as a confounding variable in the CRF stimulation test in depressed patients by comparing the frequency of FFB in the oCRF test between depressed patients and normal controls. In this study, the author examined the post-CRF secretory patterns of three HPA axis hormones( ACTH, arginine vasopressin - AVP, and cortisol) in 20 normal subjects and 36 depressed patients with a sampling schedule of plasma at three- minute intervals. |A11 three hormones demonstrated significant secretory responses to submaxial dose of oCRF(lpg/kg body weight), with AVP increasing from 1.33 土 0.70 to 7.77 土 4.17pg/ml, ACTH from 2.98 土 0.73 to 14. 52 土 1.76&11이/1111，and cortisol from 4.44 ± 0.63 to 25.93 土 1.19]Jg/dl. The two pituitary hormones showed consistent time courses of secretion, but dearly differing peak times of 19.1 and 39.5 minutes for AVP and ACTH, respectively. Cortisol began to rise after 9 minutes and peaked at 52.4 minutes. The author has illustrated the decline in plasma ACTH followed by its initial peak coinciding with the rising phase of the cortisol response in 55% of normal subjects (11/20) and 83% of depressed patients(30/36)，then a rebound of ACTH after plasma cortisol reached a high plateau level. The ACTH response to oCRF was significantly reduced by the ramp of cortisol, however, the effect of oCRF on ACTH release was more affected by the cortisol preinfusion. Conclusively, (1) the results strongly suggest that FFB in the oCRF test is common and more frequent in depressed patients than in normal subjects ； (2) FFB is a major, uncontrolled confounding variable in studies to date of the CRF stimulation procedure in depression ； (3) Pituitary gland might be the site of action of this FFB, though the author could not demonstrate this due to the confounding effect of glucocorticoid delalyed feedback inhibition