Stojilković S S, Rojas E, Stutzin A, Izumi S, Catt K J
Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
J Biol Chem. 1989 Jul 5;264(19):10939-42.
Gonadotropin-releasing hormone (GnRH) stimulates calcium mobilization and influx in pituitary gonadotrophs, and agonist-induced calcium entry through voltage-sensitive channels (VSCC) is required for the maintenance of gonadotropin secretion. However, prolonged or frequent exposure to GnRH attenuates the extracellular Ca2+-dependent cytosolic Ca2+ signal and diminishes hormone secretion. Measurements of membrane Ca2+ currents revealed significant impairment of VSCC activity in gonadotrophs during desensitization by GnRH. VSSC were also inactivated in a calcium-dependent manner during exposure to high K+. Prolonged inactivation of such Ca2+ channels by high K+ reduced the calcium and secretory responses to GnRH and vice versa. The calcium-dependent inactivation of VSCC during GnRH action appears to be a primary factor in the onset of desensitization in pituitary gonadotrophs. This mechanism could also account for the development of agonist-induced refractoriness in other calcium-regulated target cells.
促性腺激素释放激素（GnRH）刺激垂体促性腺细胞中的钙动员和内流，通过电压敏感性通道（VSCC）的激动剂诱导的钙内流是维持促性腺激素分泌所必需的。然而，长期或频繁暴露于GnRH会减弱细胞外Ca2+依赖性胞质Ca2+信号，并减少激素分泌。膜Ca2+电流测量显示，在GnRH脱敏过程中，促性腺细胞中的VSCC活性显著受损。在暴露于高K+期间，VSSC也以钙依赖的方式失活。高K+对这种Ca2+通道的长期失活降低了对GnRH的钙和分泌反应，反之亦然。GnRH作用期间VSCC的钙依赖性失活似乎是垂体促性腺细胞脱敏开始的主要因素。这种机制也可以解释其他钙调节靶细胞中激动剂诱导的不应性的发展。
