GnRH-stimulated LH release from rat anterior pituitary cells in culture: refractoriness and recovery.
Previous reports have demonstrated that long-term continuous administration of gonadotropin-releasing hormone (GnRH) to pituitary cells results in a decreased level of gonadotropin secretion. The present report demonstrates that cultured rat anterior pituitary cells preincubated for 6 h in 10(-9) or 10(-7) M GnRH became refractory to further stimulation by the releasing hormone. Cells required 2-4 days to recover from the refractory condition. Cells also became refractory to GnRH when luteinizing hormone (LH) release was blocked by Ca2+ chelation. Drugs such as veratridine, ionophore A23187, or high K+, which stimulated LH release without GnRH receptor occupancy, were also capable of causing refractoriness to GnRH in long-term exposure. These data suggest that the refractory state observed after stimulation with GnRH is a result of the combined effects of a Ca2+-independent receptor-mediated mechanism for desensitization and some other postreceptor mechanism. Tunicamycin interfered with recovery, whereas cycloheximide did not. This evidence presents a potential role for protein glycosylation in the restoration of responsiveness. Phorbol myristate acetate did not cause subsequent refractoriness to GnRH, and dibutyryl adenosine 3',5'-cyclic monophosphate had no measurable effect on the rate of recovery.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014415:Tunicamycin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D014415:Tunicamycin; D007987:Gonadotropin-Releasing Hormone; D014701:Veratridine; D007986:Luteinizing Hormone; D003513:Cycloheximide; D002118:Calcium