Glucocorticoid regulation of ACTH sensitivity of adenyl cyclase in rat fat cell membranes.
Plasma membrane sacs of isolated rat fat cells (ghots) possess an adenyl cyclase system, which is activated by lipolytic hormones of disparate molecular structure, including adrenocorticotropin (ACTH), glucagon, and epinephrine. Previous studies indicated that distinctive selectivity units for individual hormones are coupled to the same unit of adenyl cyclase in the fat cell membrane. The present study has shown that ghost cyclase from adrenalectomized and hypophysectomized rats exhibits a striking reduction in response to ACTH, the stimulatory effects of epinephrine, glucagon, or fluoride being unchanged. Pretreatment of adrenalectomized, hypophysectomized, sham operated, or intact rats with the synthetic glucocorticoid, dexamethasone, selectively increased the ACTH response in ghost cyclase preparations. Cortisol, like dexamethasone, increased the ACTH response in ghosts from adrenalectomized rats; 11-deoxycorticosterone was ineffective. The dexamethasone effect to enhance the ACTH response is blocked by actinomycin D or cycloheximide. The present results show that stimulation of rat fat cell adenyl cyclase by ACTH involves a distinctive molecular entity, which can be clearly differentiated from adenyl cyclase in the membrane as well as from the selectivity sites for epinephrine and glucagon. The data indicate that the biosynthesis of the component required for ACTH stimulation of ghost cyclase-either an ACTH selectivity unit or specific coupling factor-is induced by glucocorticoids at the level of gene regulation.
D000227:Adenine Nucleotides / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology*; D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004336:Drug Antagonism; D004798:Enzymes / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D005938:Glucocorticoids / Q000502:physiology*; D007016:Hypophysectomy; D051381:Rats; D013268:Stimulation, Chemical
D000227:Adenine Nucleotides; D004798:Enzymes; D005938:Glucocorticoids; D003609:Dactinomycin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D005934:Glucagon; D003513:Cycloheximide; D000262:Adenylyl Cyclases; D005459:Fluorides; D004837:Epinephrine