Role of chloride and inhibitory action of inorganic nitrate on gonadotropin-stimulated steroidogenesis in mouse Leydig tumor cells.
The involvement of adenylate cyclase-cyclic adenosine monophosphate (AC-cAMP) in gonadotropin-stimulated testicular steroidogenesis is well known. Little is known about the role of guanylate cyclase-cyclic guanosine monophosphate (GC-cGMP) or early chloride conductance stimulated by gonadotropins in steroidogenesis. Human chorionic gonadotropin (hCG) 1 IU/L caused significant androgen secretion without a discernible effect on cAMP production. Despite negligible intracellular cAMP, the protein kinase A inhibitor H89 blocked basal and hCG-stimulated steroidogenesis. The GC inhibitors methylene blue (MB) and LY83583 decreased androgen secretion, but hCG did not stimulate cGMP production and there was not a steroidogenic response to exogenous cGMP. A chloride-channel inhibitor, diphenylamine-2-carboxylate (DPC), at concentrations up to 0.6 mmol/L stimulated basal steroid secretion and hCG 10 IU/L stimulated cAMP production, but higher concentrations had an inhibitory effect. Substitution of chloride by gluconate enhanced basal steroid secretion, but nitrate completely abolished the effect of 1 IU/L hCG on androgen secretion, which could be partially overcome by increasing the gonadotropin concentration. In conclusion, chloride, perhaps by activating AC-cAMP, mediates the steroidogenic action of gonadotropins in mouse Leydig tumor cells (MLTC-1). Inorganic nitrate probably inhibited steroidogenesis via conversion to nitric oxide (NO) without involving the GC-cGMP pathway. Nevertheless, the results obtained with GC inhibitors suggest a role for the GC-cGMP pathway in Leydig cell steroidogenesis.
Panesar
N S
NS
Department of Chemical Pathology, Chinese University of Hong Kong, Shatin, New Territories.
D000634:Aminoquinolines / Q000494:pharmacology; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D006152:Cyclic GMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006062:Gonadotropins / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007546:Isoquinolines / Q000494:pharmacology; D007984:Leydig Cell Tumor / Q000378:metabolism*; D051379:Mice; D009566:Nitrates / Q000378:metabolism*; D013449:Sulfonamides; D013739:Testosterone / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D000634:Aminoquinolines; D000728:Androgens; D002121:Calcium Channel Blockers; D002712:Chlorides; D006063:Chorionic Gonadotropin; D004791:Enzyme Inhibitors; D006062:Gonadotropins; D007546:Isoquinolines; D009566:Nitrates; D013449:Sulfonamides; D062367:ortho-Aminobenzoates; D013739:Testosterone; C041715:6-anilino-5,8-quinolinedione; C001209:fenamic acid; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide