LH IN GNRH NEURONS DURING REPRODUCTIVE SENESCENCE

生殖衰老期间 GNRH 神经元中的 LH

• 批准号: 2859713
• 负责人: ZHENMIN LEI
• 金额: $ 6.97万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2001-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2859713
• 关键词: age difference; aging; female; gene expression; gonadotropin releasing factor; hormone receptor; hormone regulation /control mechanism; laboratory mouse; luteinizing hormone; pituitary gonadal axis; tissue /cell culture

Decreased GnRH, but increased FSH and LH levels, have been observed during reproductive aging in women and some species of laboratory animals. These paradoxical changes can not simply be explained by the dysfunctions developing in the ovary, and the mechanism remains to be determined. The facts that GnRH neurons contain LH receptors and LH inhibits GnRH synthesis and secretion lead us to postulate that LH may play a role during reproductive senescence. The underlying mechanism on the effect of LH on GnRH synthesis during reproductive aging may result from the constantly elevated LH levels that feedback on the hypothalamus where LH binds to its receptors in GnRH neurons to inhibit GnRH synthesis. Alternatively, LH receptor levels may change with age and thus the sensitivity of GnRH neurons in response to the inhibitory effect of LH may be increased. The following two specific aims are designed to test our hypothesis using several well-established cellular and molecular biology techniques. (1) To determine LH receptor levels in GnRH neurons during reproductive aging. (2) To investigate the regulation of GnRH gene expression by LH during reproductive aging. Since GnRH is at the top of the endocrine hierarchy regulating mammalian reproduction and also has a number of other physiological functions, determining the factors that contribute to age-related alteration of GnRH neuronal functions will greatly advance our current knowledge of reproductive senescence.

在女性和某些实验动物的生殖衰老期间，已经观察到GNRH降低，但FSH和LH水平升高。 这些矛盾的变化不能简单地通过卵巢中发生的功能障碍来解释，并且该机制仍有待确定。 GNRH神经元包含LH受体和LH抑制GnRH合成和分泌的事实使我们假设LH在生殖衰老过程中可能起作用。 LH在生殖衰老过程中LH对GnRH合成作用的潜在机制可能是由于LH的不断升高的水平而导致的，该水平反馈下丘脑的下丘脑LH与GNRH神经元中其受体结合以抑制GNRH的合成。 或者，LH受体水平可能随着年龄的增长而变化，因此GnRH神经元对LH抑制作用的敏感性可能会增加。 以下两个特定目标旨在使用几种完善的细胞和分子生物学技术检验我们的假设。 （1）确定生殖衰老期间GnRH神经元中的LH受体水平。 （2）研究LH在生殖衰老期间通过LH调节GnRH基因的表达。 由于GNRH位于调节哺乳动物繁殖的内分泌层次结构的顶部，并且还具有许多其他生理功能，从而确定了导致与年龄相关的GNRH神经元功能改变的因素，这将极大地促进我们当前的生殖衰老知识。