Modulation of cultured mouse Leydig cells adenylate cyclase by forskolin and hCG.
The diterpene, forskolin, stimulated cAMP accumulation about 15-fold over basal levels in purified mouse Leydig cells; however, it remained far less potent than hCG. Simultaneous addition of forskolin and hCG resulted in a striking synergistic stimulation of cAMP production. In contrast, forskolin-enhanced testosterone accumulation was never synergistic with that produced by maximal concentrations of hCG. hCG (3 X 10(-9) M) lowered about 6-fold the ED50 for forskolin-elicited cAMP accumulation and increased the maximal response to forskolin about 16-fold. Conversely, forskolin 10(-6) M) reduced the ED50 for hCG 2-fold but had a much smaller effect (2-3-fold) on maximal response. Moreover, pretreatment with hCG induced only a homologous desensitization of adenylate cyclase, whereas the enzyme became partially resistant to both hCG and forskolin in cells pretreated with forskolin. The homologous hCG-induced desensitization and the partial heterologous one induced by forskolin suggest that more than the catalytic unit of the cyclase is required for the diterpene activation.
Lefèvre
A
A
Finaz
C
C
Berthelon
M C
MC
Saez
J M
JM
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D005576:Colforsin; D000242:Cyclic AMP / Q000096:biosynthesis; D004224:Diterpenes / Q000494:pharmacology*; D004357:Drug Synergism; D004361:Drug Tolerance; D007985:Leydig Cells / Q000201:enzymology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013739:Testosterone / Q000096:biosynthesis
D006063:Chorionic Gonadotropin; D004224:Diterpenes; D005576:Colforsin; D013739:Testosterone; D000242:Cyclic AMP; D000262:Adenylyl Cyclases