Tight coupling of gonadotropin-releasing hormone receptor to stimulated phosphoinositide turnover and antigonadotropic action in granulosa cells.
Gonadotropin-releasing hormone (Gn-RH) stimulates phosphoinositide turnover by binding to its specific receptor and suppresses gonadotropin-dependent maturation and steroidogenesis in granulosa cells. This study was undertaken to determine whether persistent receptor occupancy was necessary for Gn-RH to exert such actions on rat granulosa cells, or whether Gn-RH actions were continued by a first and transient stimulation by Gn-RH, using a competitive antagonist, antide. Gn-RH stimulated [32P]phosphate incorporation into phosphatidylinositol (PtdIns), which could be terminated by displacement of previously bound Gn-RH from its receptor by antide and restarted by reoccupying the receptors with Gn-RH. Antide could prevent Gn-RH-stimulated PtdIns radiolabelling whenever it was added to incubations. An identical effect of antide was observed also in the anti-follicle-stimulating hormone (FSH) action of Gn-RH. FSH markedly stimulated aromatase activity, and Gn-RH caused a time- and dose-dependent inhibition of FSH action. Estrogen production was quenched by Gn-RH and restarted at a time when Gn-RH was removed from its receptor by antide. These two responses associated with the occupancy of Gn-RH receptor provide the evidence in favor of a tight coupling of stimulated PtdIns turnover to suppression of aromatase activation. These data of required continued activation of receptor might exclude the possibility that hypothalamic Gn-RH participated in the control of steroidogenesis in the ovary.
Imai
A
A
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Japan.
Iida
K
K
Tamaya
T
T
D000818:Animals; D001667:Binding, Competitive; D003470:Culture Media; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006728:Hormones / Q000494:pharmacology; D066298:In Vitro Techniques; D008954:Models, Biological; D009842:Oligopeptides / Q000494:pharmacology*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011966:Receptors, LHRH / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical
D003470:Culture Media; D006728:Hormones; D009842:Oligopeptides; D010716:Phosphatidylinositols; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; C057022:iturelix