Desensitization of pituitary gonadotropes by mediators of LH release.
Desensitization of pituitary gonadotropes by exposure to 10 nM gonadotropin-releasing hormone (GnRH) for 6 h severely impaired the luteinizing hormone (LH) response to a second 3-h treatment with GnRH, and reduced the secretory responses to 50 microM arachidonic acid (AA), 100 nM tetradecanoyl phorbol-13-acetate (TPA), and AA + TPA. Pretreatment with AA blocked subsequent responses to AA but not to other secretagogues. Pretreatment with TPA attenuated the LH response to TPA, but not to GnRH, AA, and AA + TPA. After exposure to AA + TPA, all subsequent responses were abolished. Each of the secretagogues reduced GnRH receptor binding, but only GnRH-induced receptor loss and desensitization were reversed by simultaneous incubation with a GnRH antagonist. Similar results were obtained when 16-h pretreatment periods were used, or when the data were normalized for the concomitant reduction of cellular LH content. These findings indicate that GnRH-receptor loss and depletion of LH content are not the sole causes of GnRH-induced desensitization. Receptor uncoupling and impairment of AA- and protein kinase C-dependent pathways may also be involved in this process.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D013755:Tetradecanoylphorbol Acetate