Etiology of the differences in corticotropin-releasing hormone-induced adrenocorticotropin secretion of black and white women.
After i.v. oCRH, plasma immunoreactive ACTH (ACTH-IR) is significantly greater in blacks than in whites; however, there is no corresponding increase in cortisol secretion. To test the hypothesis that there are black-white differences in adrenal responsiveness to ACTH that underlie this phenomenon, weight-, age-, and education-matched black (n = 10) and white (n = 10) women were i.v. infused with 5 differing doses of ACTH1-24 (0, 0.003, 0.01, 0.1, and 1 microgram/kg) with measured plasma cortisol and DHEA. To test the alternative hypothesis that greater post-CRH plasma ACTH-IR in blacks is caused by qualitative differences in circulating ACTH-immunoreactive peptides, we collected pre- and post-CRH plasma from 5 black and 5 white women and measured ACTH-IR after sample fractionation, using high-pressure liquid chromatography. There were no racial differences in adrenal responsiveness to differing doses of ACTH1-24 and no differences in the distribution of the forms of ACTH-IR before CRH. After CRH, whites had predominant ACTH-IR peaks at the retention times of ACTH1-39 and ACTH1-39-sulfoxide, whereas blacks had prominent peaks at several additional retention times. The post-CRH ratio of intact to total ACTH was significantly lower in blacks than in whites (0.27 +/- 0.17 vs. 0.71 +/- 0.17, P < 0.003). We conclude that there are qualitative differences in post-CRH circulating ACTH-IR in blacks and whites, leading to a greater immunoreactive to bioactive ACTH ratio in blacks. Such differences in the circulating forms of ACTH can account for greater CRH-stimulated ACTH-IR in blacks.
Yanovski
J A
JA
Clinical Center, National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Yanovski
S Z
SZ
Friedman
T C
TC
Loh
Y P
YP
Jayasvasti
V
V
Cutler
G B
GB
Chrousos
G P
GP
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000328:Adult; D044383:Black People; D002851:Chromatography, High Pressure Liquid; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003687:Dehydroepiandrosterone / Q000097:blood; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007700:Kinetics; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D044465:White People
D010446:Peptide Fragments; D003687:Dehydroepiandrosterone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone