Mechanism of glucocorticoid enhancement of the responsiveness of ovine adrenocortical cells to adrenocorticotropin.
The present studies were undertaken to precise the mechanism through which glucocorticoids enhance the responsiveness of ovine adrenocortical cells to ACTH. Experiments using intact cells and crude adrenal membranes have shown that, at the level of the adenylate cyclase system, dexamethasone increases the number of ACTH receptors without modification of the catalytic subunit or of the GTP binding regulatory components Gs and Gi. Cells cultured with dexamethasone secreted more pregnenolone and more corticosteroids in response to 8-BrcAMP than did control cells. By contrast, dexamethasone did not increase corticosterone secretion by cells incubated in the presence of 22-(R)-hydroxycholesterol or of exogenous pregnenolone. Dexamethasone neither affected the incorporation of [14C] acetate into cellular cholesterol nor the amount of cholesterol present in mitochondria of unstimulated cells. However, dexamethasone-treated cells incubated in the presence of both 8-BrcAMP and aminoglutethimide exhibited higher amounts of mitochondrial cholesterol than control cells. These data indicate that dexamethasone enhances the number of cellular ACTH receptors together with increasing the cAMP-induced translocation of cholesterol from the cytoplasm into mitochondria and/or mitochondrial storage of cholesterol.
Darbeida
H
H
INRA, URA CNRS 1291, Mønnaie, France.
Durand
P
P
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000085:Acetates / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D002784:Cholesterol / Q000096:biosynthesis*; D005576:Colforsin / Q000494:pharmacology; D003345:Corticosterone / Q000096:biosynthesis*; D003366:Cosyntropin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism*; D004357:Drug Synergism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007700:Kinetics; D011284:Pregnenolone / Q000096:biosynthesis* / Q000494:pharmacology; D012756:Sheep; D012969:Sodium Fluoride / Q000494:pharmacology
D000085:Acetates; D003366:Cosyntropin; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D006165:Guanylyl Imidodiphosphate; D011284:Pregnenolone; D003907:Dexamethasone; D012969:Sodium Fluoride; D002772:Cholera Toxin; D002784:Cholesterol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D003345:Corticosterone