Blunted adrenocorticotropin but normal beta-endorphin release after human corticotropin-releasing hormone administration in depression.
Since the discovery of CRH in 1981, several investigators have reported abnormalities of the hypothalamic-pituitary-adrenal (HPA) system in response to direct stimulation of the corticotroph cells in patients with psychiatric disorders. To further explore HPA system integrity in major depressive disorders, 13 drug-free patients and normal subjects matched for age, sex, ovarian status, and body weight received 100 micrograms synthetic human CRH as an iv bolus dose. Compared to that in the normal subjects, in the depressed patients a significant attenuation of the net ACTH release after CRH administration (772 +/- 597 vs. 263 +/- 286 pmol/min.L; P less than 0.02) was observed, while beta-endorphin and cortisol responses did not differ significantly between the groups. The magnitudes of ACTH and cortisol release were negatively correlated in the patient group only (r = -0.67; P less than 0.01). Thus, the blunted ACTH response to CRH in depression might be related to hypercortisolemia, while the implications of the apparent dissociation of ACTH and beta-endorphin after CRH administration still remain unclear. Our data support the hypothesis that the hyperactivity of the HPA system in depression most likely is a consequence of CRH hypersecretion, the origin of which may be explained by abnormal central glucocorticoid receptor or neurotransmitter regulation.
Rupprecht
R
R
Psychiatrische Klinik, University of Würzburg, West Germany.
Lesch
K P
KP
Müller
U
U
Beck
G
G
Beckmann
H
H
Schulte
H M
HM
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000328:Adult; D003346:Corticotropin-Releasing Hormone; D003866:Depressive Disorder / Q000097:blood*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D012016:Reference Values; D001615:beta-Endorphin / Q000097:blood / Q000378:metabolism*
D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone