Angiotensin stimulation of adrenal fasciculata cells.
In this paper we provide evidence to show that the pathways by which adrenocorticotropic hormone (ACTH) and angiotensin II (AII) stimulate steroidogenesis in bovine fasciculata cells are only partially independent. Both hormones have the same intrinsic activity but a 500-fold higher dose of AII is required to achieve 50% stimulation of steroidogenesis. Whereas ACTH acts by way of cAMP, AII appears to operate through protein kinase C. The phorbol ester, 12-O-tetradecanoylphorbol-13 acetate (TPA), and the calcium ionophore, A23187, each stimulate steroidogenesis and, when added together, act synergistically. To test the relationship between the ACTH and AII pathways, we added the two hormones simultaneously and measured steroid production. When the hormones were present at submaximal concentrations, their effects were additive. At maximal doses, steroid production was 40% above that elicited by either hormone alone. In contrast to the action of AII in the glomerulosa cell where it inhibits ACTH-stimulated cAMP formation, AII causes no inhibition in the fasciculata. Cycloheximide inhibits steroidogenesis stimulated by AII or a mixture of TPA and A23187. Scatchard analysis of the binding of 125I-AII to particulates from adrenal cortical fasciculata indicates the presence of a single class of binding sites (Kd = 0.6 X 10(-8) M). Binding is not inhibited by ACTH. Biotin-containing AII analogs that bind specifically to the particulates have been evaluated as potential tools for avidin-biotin affinity chromatography of the receptor. One of these, [N epsilon-6-(biotinylamido)hexyllys1, Val5] AII, is a promising candidate for receptor isolation.
Finn
F M
FM
Protein Research Laboratory, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Stehle
C
C
Ricci
P
P
Hofmann
K
K
D000302:Adrenal Cortex / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D005938:Glucocorticoids / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000032:analysis
D005938:Glucocorticoids; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D011493:Protein Kinase C