AJP - Endocrinology and Metabolism, Vol 249, Issue 6 619-E625, Copyright © 1985 by American Physiological Society

ARTICLES

GnRH-stimulated LH release from rat anterior pituitary cells in culture: refractoriness and recovery

H. A. Jinnah and P. M. Conn

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.

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				C. A. McArdle, G. B. Willars, R. C. Fowkes, S. R. Nahorski, J. S. Davidson, and W. Forrest-Owen Desensitization of Gonadotropin-releasing Hormone Action in alpha T3-1 Cells Due to Uncoupling of Inositol 1,4,5-Trisphosphate Generation and Ca2+ Mobilization J. Biol. Chem., September 27, 1996; 271(39): 23711 - 23717. [Abstract] [Full Text] [PDF]