DESENSITIZATION OF LH SECRETION BY GNRH

GNRH 对 LH 分泌的脱敏作用

• 批准号: 2026196
• 负责人: JIMMY D NEILL
• 金额: $ 25.83万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-10 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2026196
• 关键词: G protein; enzyme activity; glutathione transferase; gonadotropin releasing factor; hormone regulation /control mechanism; inositol phosphates; laboratory rabbit; laboratory rat; luteinizing hormone; pituitary gland; secretion; tissue /cell culture

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.

描述（改编自研究者摘要）：脱敏 促性腺激素分泌LH是GnRH作用的标志，除非它是 以脉动的方式给予或分泌。 的细胞和分子 促性腺激素脱敏的机制知之甚少。 一类 最初在酵母中发现的蛋白质被描述为 参与了哺乳动物细胞脱敏。 称为G蛋白调节器 信号传导（RGS），这些蛋白质之一（RGS-3）已被我们证明， 抑制GnRH刺激细胞三磷酸肌醇（IP 3）水平， mRNA存在于促性腺激素aT 3 -1细胞系中，RGS通过免疫荧光法检测。 aT 3 -1和垂体细胞膜中的抗体。 RGS 3显示结合 Gqa蛋白在体外支持RGSs通过结合G 蛋白质，从而抑制受体与G蛋白偶联， 磷脂酶C激活。 15个编码RGSs的哺乳动物基因已经被 鉴定 具体目标是：（1）完成初步 将RGS 3表征为参与GnRH诱导的脱敏; (2)确定15名RGS家族成员中的其他成员是否参与了 从GnRH处理的aT 3 -1细胞中筛选RNA诱导GnRH脱敏 (3)探讨RGS在GnRH诱导的LH脱敏中的作用 纯化的大鼠垂体促性腺激素分泌。 这些实验 可能提供GnRH诱导的细胞和分子解释 脱敏，也许提供了一个更广泛的问题， 一般促性腺激素反应性的调节。