DESENSITIZATION OF LH SECRETION BY GNRH

描述(改编自调查者摘要)：脱敏 促性腺激素分泌的黄体生成素是促性腺激素释放激素作用的标志，除非它是 脉动的以脉动的方式管理或分泌的细胞和分子 促性腺激素脱敏的机制尚不清楚。一类人 最初在酵母中发现的蛋白质被描述为 参与哺乳动物细胞脱敏。被称为G蛋白的调节剂 信号转导(RGS)，其中一种蛋白(RGS-3)已经被我们发现 抑制促性腺激素释放激素刺激的细胞三磷酸肌醇(IP3)水平，其 在促性腺激素AT3-1细胞系中存在mRNA，RGS通过 AT3-1和垂体细胞膜上的抗体。RGS3显示为绑定 GqA蛋白在体外支持RGSS通过结合G起作用的观点 蛋白质，从而抑制G蛋白偶联的受体 磷脂酶C激活。编码RGSS的15个哺乳动物基因已经被 已确认身份。具体目标是：(1)完成前期工作 RGS3参与促性腺激素释放激素诱导的脱敏； (2)确定RGS家族15个成员中的其他成员是否参与 从经GnRH处理的AT3-1细胞中筛选RNA以诱导GnRH脱敏； (3)探讨RGS在促性腺激素释放激素(GnRH)促黄体生成素脱敏中的作用 纯化的大鼠垂体促性腺激素的分泌。这些实验有 为促性腺激素释放激素诱导提供细胞和分子解释的可能性 脱敏，也许提供了一个更广泛的问题的入口 一般促性腺激素反应性的调节。

DESCRIPTION (Adapted from the Investigator's Abstract): Desensitization of LH secretion by the gonadotrope is a hallmark of GnRH action unless it is administered or secreted in a pulsatile fashion. The cellular and molecular mechanisms of gonadotrope desensitization is poorly understood. A class of proteins discovered originally in yeast have been described as being involved in mammalian cell desensitization. Called regulators of G-protein signalling (RGS), one of these proteins (RGS-3) has been shown by us to inhibit GnRH-stimulated cellular inositol trisphosphate (IP3) levels, its mRNA is present in the gonadotropic aT3-1 cell line, and RGS is detected by antibodies in membranes of aT3-1 and pituitary cells. RGS3 is shown to bind the Gqa protein in vitro supporting the notion that RGSs act by binding G proteins, thus inhibiting G-protein coupling of the receptor to phospholipase C activation. Fifteen mammalian genes encoding RGSs have been identified. The Specific Aims are to: (1) complete the preliminary characterization of RGS3 as participating in GnRH-induced desensitization; (2) Determine if other members of the 15 member RGS family are involved in GnRH-induced desensitization by screening RNA from GnRH-treated aT3-1 cells; (3) Investigate the role of RGS in GnRH-induced desensitization of LH secretion in purified rat pituitary gonadotropes. The experiments have the potential to provide a cellular and molecular explanation of GnRH-induced desensitization, and perhaps provide an entree to the wider issue of regulation of general gonadotrope responsiveness.