Hormonal antagonistic properties of chemically deglycosylated human choriogonadotropin.
The biological properties of chemically deglycosylated human choriogonadotropin (DG-hCG) preparations were examined in collagenase-dispersed rat interstitial cells in vitro. Despite effective receptor binding activity in membrane preparations, DG-hCG failed to induce cyclic AMP accumulation in the cells when incubated in the presence or absence of a phosphodiesterase inhibitor. The steroidogenic ability as assessed by testosterone accumulation in the medium was less than 0.5% of the native hormone with a failure to attain maximal steroid production. Time course experiments have revealed that altered kinetics could not be responsible for the loss of hormone response. Consistent with its property of good receptor binding and poor cell activation, DG-hCG antagonized the action of native hCG. When added to the cells at the same time, DG-hCG inhibited the action of a maximal stimulatory dose of hCG in a dose-dependent manner. Inhibition of cyclic AMP accumulation was complete whereas inhibition of steroidogenesis was about 75%. DG-hCG had no effect on the stimulatory action of cholera toxin in interstitial cells or that of follitropin in rat seminiferous tubular preparations. The data suggest that DG-hCG has a conformation conductive for effective interaction with the receptor, but its ability to activate the adenylate cyclase is either lost or weakly expressed.
D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D006063:Chorionic Gonadotropin / Q000378:metabolism* / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004336:Drug Antagonism; D005260:Female; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D010053:Ovary / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011974:Receptors, LH; D012671:Seminiferous Tubules / Q000187:drug effects / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis; D013737:Testis / Q000187:drug effects / Q000378:metabolism*
D006063:Chorionic Gonadotropin; C034923:HCG, deglycosylated; D011956:Receptors, Cell Surface; D011974:Receptors, LH; D013256:Steroids; D007986:Luteinizing Hormone; D002772:Cholera Toxin; D000242:Cyclic AMP