Jinnah H A, Conn P M
Am J Physiol. 1985 Dec;249(6 Pt 1):E619-25. doi: 10.1152/ajpendo.1985.249.6.E619.
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.
先前的报告表明，对垂体细胞长期持续给予促性腺激素释放激素（GnRH）会导致促性腺激素分泌水平降低。本报告表明，在10⁻⁹或10⁻⁷M GnRH中预孵育6小时的培养大鼠垂体前叶细胞对释放激素的进一步刺激变得不敏感。细胞需要2 - 4天才能从不应期恢复。当通过Ca²⁺螯合阻断促黄体生成素（LH）释放时，细胞对GnRH也变得不敏感。诸如藜芦碱、离子载体A23187或高K⁺等药物，在未占据GnRH受体的情况下刺激LH释放，长期暴露时也能够导致对GnRH的不应性。这些数据表明，GnRH刺激后观察到的不应期状态是Ca²⁺非依赖性受体介导的脱敏机制和一些其他受体后机制共同作用的结果。衣霉素干扰恢复，而环己酰亚胺则没有。这一证据表明蛋白质糖基化在恢复反应性方面具有潜在作用。佛波酯不会导致随后对GnRH的不应性，二丁酰腺苷3',5'-环一磷酸对恢复速率没有可测量的影响。
