Inhibition of hormone-induced cyclic AMP production and steroidogenesis in interstitial cells by deglycosylated lutropin.
We have investigated the ability of chemically deglycosylated ovine pituitary lutropin (DGLH) to stimulate cyclic AMP accumulation in rat interstitial cells in vitro. In sharp contrast to the native hormone which brought about a large increase in cyclic AMP levels, no significant response was indiced by DGLH even in the presence of the phosphodiesterase inhibitor, isobutyl methylxanthine. On the contrary, all preparations of DGLH tested were potent inhibitors of the action of the native hormone. The concentration of DGLH for inhibition of LH-induced cyclic AMP response was significantly lower than that required for inhibition of steroidogenesis. While inhibition of hormone-induced cyclic AMP response was complete, the inhibition of steroidogenesis in testicular cells by DGLH approached about 70-80%. Accumulation of cycli AMP induced by hCG was also effectively inhibited by DGLH suggesting that its inhibitory action is mediated via its binding to lutropin receptor(s) on interstitial cells. A recombinant of deglycosylated subunits, DG alpha + DG beta, had properties identical to that of DGLH.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002772:Cholera Toxin; D006063:Chorionic Gonadotropin / Q000037:antagonists & inhibitors; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D051381:Rats; D013739:Testosterone / Q000096:biosynthesis*
D006063:Chorionic Gonadotropin; C030405:luteinizing hormone, deglycosylated; D013739:Testosterone; D007986:Luteinizing Hormone; D002772:Cholera Toxin; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine