Effects of glucocorticoid antagonism with RU 486 on pituitary-adrenal function in patients with major depression: time-dependent enhancement of plasma ACTH secretion.
Data from our group and others suggest that pituitary-adrenal activation in major depression reflects a defect at or above the hypothalamus which results in the hypersecretion of corticotropin-releasing hormone (CRH); some have suggested, however, that elevated indices of cortisol secretion and lack of suppressibility to dexamethasone may be a manifestation of a primary defect in glucocorticoid receptor activation. We report here a study of early morning pituitary-adrenal responses to the glucocorticoid antagonist RU 486 in patients with major depression and healthy volunteers. Previous data suggested that the response to RU 486 could represent an index of endogenous CRH secretory activity. RU 486 produced a robust increase in plasma corticotropin (ACTH) and cortisol secretion in both control subjects and depressed patients. In the controls, however, the increase was confined to the last 2 hours of sampling (6 to 8 am), whereas in the depressed patients the increase occurred throughout the sampling period (3 to 8 am). The ACTH response in the depressed patients exceeded that in the controls during most of the sampling period, including a significant (p less than .005) increase between 3 and 4:30 am. These results are compatible with the idea that hypercortisolism in major depression represents an alteration in the overall set point for hypothalamic CRH secretion rather than a primary alteration at the level of the glucocorticoid receptor.
Kling
M A
MA
Whitfield
H J
HJ
Brandt
H A
HA
Demitrack
M A
MA
Kalogeras
K
K
Geracioti
T D
TD
Perini
G I
GI
Calabrese
J R
JR
Chrousos
G P
GP
Gold
P W
PW
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D003866:Depressive Disorder / Q000503:physiopathology*; D005260:Female; D005938:Glucocorticoids / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D010912:Pituitary-Adrenal Function Tests; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D013997:Time Factors
D005938:Glucocorticoids; D015735:Mifepristone; D000324:Adrenocorticotropic Hormone