Protein kinase C activity can desensitize the gonadotropin-responsive adenylate cyclase in Leydig tumor cells. But hCG-induced desensitization does not involve protein kinase C activation.
The murine Leydig tumor cell line, MLTC-1, contains a gonadotropin receptor-coupled adenylate cyclase. Although the binding of human choriogonadotropin (hCG) initially causes cells to accumulate cAMP, in time, the response to hCG is attenuated by desensitization. Treating intact cells with the tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), or with diacylglycerol also causes desensitization of the hCG response. These compounds are activators of calcium/phospholipid-dependent protein kinase (PKC). Treating MLTC-1 cells with TPA or dioctanoylglycerol increased the portion of PKC in the cell membrane fraction. This phenomenon is associated with activation of PKC. Treating isolated membranes with purified PKC desensitize the hCG response. Thus, desensitization caused by TPA or dioctanoylglycerol is probably mediated by PKC. PKC is normally activated when phosphoinositides are metabolized to diacylglycerol and inositol phosphates. There was no significant accumulation of inositol phosphates when cells were treated with hCG. hCG did not increase the portion of PKC in the cell membrane fraction. However, hCG could desensitize isolated membranes, but TPA could not. We conclude that although protein kinase C activity can desensitize the gonadotropin response, hCG does not cause desensitization by activating PKC. The implications of this observation are discussed.
Inoue
Y
Y
Laboratory of Molecular and Cellular Neurobiology, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892.
Rebois
R V
RV
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation; D007294:Inositol / Q000378:metabolism; D007700:Kinetics; D007984:Leydig Cell Tumor / Q000201:enzymology*; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D006063:Chorionic Gonadotropin; D004075:Diglycerides; C044295:1,2-dioctanoylglycerol; D015240:Phorbol 12,13-Dibutyrate; D007294:Inositol; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate