Effects of corticostatin-I on rat adrenal cells in vitro.
We have examined the mechanism by which corticostatin-I (CS-I) acts to attenuate ACTH-induced steroidogenesis in rat adrenal cells. CS-I inhibited ACTH-induced corticosterone production in a dose-dependent manner, without any effects on the basal corticosterone level in adrenal cells. When the cells were stimulated by 100 pg ACTH/ml, the minimum effective concentration of CS-I was 100 ng/ml, and 0.3-1.0 micrograms CS-I/ml produced a 50% reduction of the stimulated corticosterone production. The inhibitory effect of CS-I on ACTH-stimulated corticosterone production became apparent within 15 min of incubation, and the effect was reversed quickly by the removal of CS-I from the media. CS-I had no effect on angiotensin II-stimulated aldosterone production by adrenal zona glomerulosa cells. CS-I also did not affect cyclic AMP- or forskolin-stimulated corticosterone production. In an in-vitro binding study using 125I-labelled CS-I, CS-I showed considerable specific binding to rat adrenal cells, and the binding competed with ACTH in a dose-dependent manner. These experiments suggest that CS-I competes with ACTH on their binding sites and exerts an inhibitory effect on the adrenal cells.
Tominaga
T
T
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Fukata
J
J
Naito
Y
Y
Nakai
Y
Y
Funakoshi
S
S
Fujii
N
N
Imura
H
H
D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D003345:Corticosterone / Q000096:biosynthesis; D023082:Defensins; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009504:Neutrophils / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical
D001798:Blood Proteins; D023082:Defensins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C054598:corticostatin; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone