促卵泡激素抑制蛋白（FSP）对培养的大鼠垂体前叶细胞中促性腺激素释放激素刺激的促性腺激素分泌的急性抑制作用。

Acute inhibitory effect of follicle-stimulating hormone-suppressing protein (FSP) on gonadotropin-releasing hormone-stimulated gonadotropin secretion in cultured rat anterior pituitary cells.

作者信息

Wang Q F, Farnworth P G, Burger H G, Findlay J K

机构信息

Prince Henry's Institute of Medical Research, South Melboure, Victoria, Australia.

出版信息

Mol Cell Endocrinol. 1990 Jul 30;72(1):33-42. doi: 10.1016/0303-7207(90)90237-3.

DOI:10.1016/0303-7207(90)90237-3

PMID:2125565

Abstract

Follicle-stimulating hormone (FSH)-suppressing protein (FSP) or follistatin, a novel gonadal glycoprotein hormone, has been shown to have chronic inhibitory effects on the secretion of both FSH and luteinizing hormone (LH) in response to gonadotropin-releasing hormone (GnRH) in vitro. The present study was designed to investigate the acute effects of bovine FSP on GnRH-stimulated gonadotropin secretion and to examine the potential subcellular sites of this action of FSP using cultured pituitary cells. Anterior pituitaries from adult male Sprague-Dawley rats were enzymatically dispersed and cultured for 48 h, after which the cells were treated with bovine FSP for 6 h, followed by a 4 h stimulation with secretagogues in the continued presence of FSP. Results showed that the 35 kDa form of bovine FSP (0.1-3 nM) dose-dependently suppressed GnRH-stimulated FSH and LH secretion, with inhibition of 38 and 25%, respectively, at 3 nM. In addition, FSP suppressed gonadotropin secretion in response to activators of protein kinase C (phorbol 12-myristate 13-acetate (PMA) and mezerein) and a calcium ionophore (A23187). However, FSP had no effect on gonadotropin secretion evoked by melittin, an activator of phospholipase A2. Furthermore, 35 kDa bovine FSP did not compete with GnRH for GnRH binding sites in a direct competition study and treatment of cultured pituitary cells with FSP (0.1-3 nM) for 10 h did not alter the number of GnRH binding sites on the cell membranes. Finally, similar inhibitory effects on gonadotropin secretion in response to GnRH, PMA and mezerein were obtained with the 31 and 39 kDa forms of bovine FSP, each at a concentration of 1 nM. We conclude from the present study that FSP acutely inhibits GnRH-stimulated gonadotropin secretion in cultured pituitary cells, and that FSP exerts its action beyond the GnRH receptor, possibly by affecting the protein kinase C and/or the calcium-calmodulin systems.

摘要

卵泡刺激素（FSH）抑制蛋白（FSP）即卵泡抑素，是一种新型性腺糖蛋白激素，已证实在体外对促性腺激素释放激素（GnRH）刺激下的FSH和黄体生成素（LH）分泌具有慢性抑制作用。本研究旨在探讨牛FSP对GnRH刺激的促性腺激素分泌的急性影响，并利用培养的垂体细胞研究FSP这一作用的潜在亚细胞位点。将成年雄性Sprague-Dawley大鼠的垂体前叶进行酶解分散并培养48小时，之后用牛FSP处理细胞6小时，然后在FSP持续存在的情况下用促分泌剂刺激4小时。结果显示，35 kDa形式的牛FSP（0.1 - 3 nM）呈剂量依赖性地抑制GnRH刺激的FSH和LH分泌，在3 nM时分别抑制38%和25%。此外，FSP抑制了对蛋白激酶C激活剂（佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）和大戟二萜醇）以及钙离子载体（A23187）的促性腺激素分泌反应。然而，FSP对磷脂酶A2激活剂蜂毒素诱发的促性腺激素分泌没有影响。此外，在直接竞争研究中，35 kDa牛FSP不与GnRH竞争GnRH结合位点，用FSP（0.1 - 3 nM）处理培养的垂体细胞10小时也未改变细胞膜上GnRH结合位点的数量。最后，31 kDa和39 kDa形式的牛FSP在浓度为1 nM时，对GnRH、PMA和大戟二萜醇刺激的促性腺激素分泌具有类似的抑制作用。我们从本研究得出结论，FSP急性抑制培养的垂体细胞中GnRH刺激的促性腺激素分泌，并且FSP在GnRH受体之外发挥作用，可能是通过影响蛋白激酶C和/或钙 - 钙调蛋白系统。