Responses of Y1 adrenocortical tumor cells to o-nitrophenyl sulfenyl ACTH.
NPS(o-nitrophenyl sulfenyl)-ACTH stimulated steroidogenesis in Y1 cells to the same maximum level as did ACTH, but with a 60-fold lower potency than the native hormone. NPS-ACTH also stimulated the extracellular accumulation of cAMP in Y1 cells with lower potency than the unmodified hormone. The amount of cAMP accumulated in the presence of NPS-ACTH approached 75% of the maximum with ACTH. In Y1 plasma membranes, NPS-ACTH was a partial agonist of adenylate cyclase activity, witn an efficacy dependent upon the type of guanyl nucleotide present. The steroidogenic responses of two Y1(Kin) mutants and two Y1(Cyc) mutants to NPS-ACTH paralleled their responses to ACTH and reflected closely their defects in cAMP-dependent protein kinase and ACTH-sensitive adenylate cyclase activity. These data imply an obligatory role for adenylate cyclase and cAMP-dependent protein kinase activities in stimulation of steroidogenesis in Y1 cells by NPA-ACTH.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000306:Adrenal Cortex Neoplasms / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002999:Clone Cells; D000242:Cyclic AMP / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis
C024813:ACTH, 2-nitrophenylsulfenyl-; D013256:Steroids; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D011494:Protein Kinases; D000262:Adenylyl Cyclases