Wang Q F, Farnworth P G, Findlay J K, Burger H G
Medical Research Centre, Prince Henry's Hospital, Melbourne, Victoria, Australia.
Endocrinology. 1988 Nov;123(5):2161-6. doi: 10.1210/endo-123-5-2161.
The mechanism by which inhibin decreases the responsiveness of the pituitary gonadotroph to GnRH in terms of secretion of gonadotropins is largely unknown. We studied the effect of pure 31K bovine inhibin on the specific binding of GnRH to rat anterior pituitary cells in culture using iodinated Buserelin as tracer. Results showed that treatment of cultured anterior pituitary cells from adult male rats with inhibin (0-30 U/ml) for 72 h decreased Buserelin binding in a dose-dependent manner. In the presence of a maximally inhibiting dose of manner. In the presence of a maximally inhibiting dose of inhibin, Buserelin binding decreased progressively with time, reaching a minimum of 42% of the control value after 3 days. Exposure of pituitary cells for 3 days to the inhibin-related peptides transforming growth factor-beta (up to 400 pM) and Müllerian inhibitory substance (up to 100 nM) did not decrease binding of Buserelin, suggesting that the effect was specific to inhibin. Inhibin did not compete with iodinated Buserelin for GnRH-binding sites when they were added to the assay tube simultaneously. In addition, treatment with inhibin halved the number, but did not change the affinity, of GnRH-binding sites and had no effect on either cell number of cell viability. It is concluded that the reduction by inhibin of rat gonadotroph responsiveness to GnRH may be partly related to a decrease in the number of GnRH receptors on the cell surface.
抑制素通过何种机制降低垂体促性腺细胞对促性腺激素释放激素(GnRH)的反应性,进而减少促性腺激素的分泌,目前尚不清楚。我们使用碘化布舍瑞林作为示踪剂,研究了纯31K牛抑制素对培养的大鼠垂体前叶细胞中GnRH特异性结合的影响。结果显示,用抑制素(0 - 30 U/ml)处理成年雄性大鼠培养的垂体前叶细胞72小时,布舍瑞林结合呈剂量依赖性降低。在存在最大抑制剂量的抑制素的情况下,布舍瑞林结合随时间逐渐降低,3天后降至对照值的42%。将垂体细胞暴露于抑制素相关肽转化生长因子-β(高达400 pM)和苗勒管抑制物质(高达100 nM)3天,并未降低布舍瑞林的结合,这表明该作用对抑制素具有特异性。当抑制素与碘化布舍瑞林同时添加到测定管中时,抑制素并不与碘化布舍瑞林竞争GnRH结合位点。此外,抑制素处理使GnRH结合位点数量减半,但不改变其亲和力,并且对细胞数量或细胞活力均无影响。结论是,抑制素降低大鼠促性腺细胞对GnRH的反应性可能部分与细胞表面GnRH受体数量减少有关。