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.

在女性和某些实验室动物的生殖老化过程中，观察到GnRH水平降低，但FSH和LH水平升高。 这些矛盾的变化不能简单地用卵巢功能障碍来解释，其机制仍有待确定。 GnRH神经元含有LH受体，LH抑制GnRH的合成和分泌，这一事实使我们推测LH可能在生殖衰老过程中发挥作用。 生殖衰老过程中LH对GnRH合成影响的潜在机制可能是由于LH水平不断升高，反馈下丘脑，LH与GnRH神经元中的受体结合，抑制GnRH合成。 另外，LH受体水平可能随年龄而变化，因此GnRH神经元对LH抑制作用的敏感性可能增加。 以下两个具体目标旨在使用几种成熟的细胞和分子生物学技术来测试我们的假设。 (1)探讨生殖衰老过程中GnRH神经元LH受体水平的变化。 (2)探讨生殖衰老过程中LH对GnRH基因表达的调节作用。 由于GnRH处于调节哺乳动物生殖的内分泌层次的顶端，并且还具有许多其他生理功能，因此确定促性腺激素释放激素神经元功能与年龄相关的改变的因素将极大地推进我们目前对生殖衰老的认识。