FSH, Estradiol and Inhibin in Female Reproduction

FSH、雌二醇和抑制素对女性生殖的影响

• 批准号: 6531795
• 负责人: JANET E HALL
• 金额: $ 35.03万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-10 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6531795
• 关键词: African American; aging; aromatase; caucasian American; clinical research; enzyme activity; estradiol; female; female reproductive system disorder; fertility; follicle stimulating hormone; gene expression; gonadotropin releasing factor; granulosa cell; hormone regulation /control mechanism; human subject; hypothalamic pituitary axis; hypothalamus; inhibin; intermolecular interaction; luteinizing hormone; menstrual cycle; ovulation; postmenopause; racial /ethnic difference; secretion; women's health

The broad goal of this project is to continue to investigate the neuroendocrine and gonadal regulation of reproduction in women, focusing on the complex interrelationships between FSH, estradiol and the inhibins. There is now evidence that both estradiol and the inhibins contribute to the negative feedback control of FSH in women. However, their relative roles in the precise control of FSH during the follicular and luteal phases of the normal menstrual cycle have not been delineated. There are two unique circumstances in which we have shown that the coordinated secretion of estradiol and the inhibins is altered: in reproductive aging, estradiol levels are increased in the presence of low levels of inhibin while in African-American women, normal reproductive cycles are characterized by increased estradiol relative to Caucasian women in the face of identical levels of inhibin. Determining the mechanisms responsible for these changes will provide us with important insights into the interactions of inhibin, estradiol and gonadotropins in normal reproductive physiology. Aim 1 will determine the relative contributions of estradiol and the inhibins to the negative feedback regulation of FSH secretion during the follicular and luteal phases of the normal menstrual cycle using normal and GnRH-deficient women in whom estrogen secretion is altered by aromatase blockade. Aim 2 will seek to elucidate the mechanisms underlying the dichotomy between estradiol and inhibin secretion in reproductive aging by investigating inhibin and estradiol secretion in response to fixed FSH stimulation and by determining the number of granulosa cells and inhibin subunit expression and aromatase function and expression in antral and preovulatory follicles as a function of reproductive aging. Aim 3 will determine the feedback and feed-forward interactions between FSH, estradiol and the inhibins that result in an increase in estradiol levels across normal reproductive cycles in African- American women. Feedback will be examined using an estrogen infusion protocol while feed-forward will examine the control of estradiol and inhibin secretion in preovulatory follicles. Understanding the feedback and feed-forward dynamics of the hypothalamic-pituitary and ovarian components of the reproductive system is critical to an appreciation of the pathophysiology of reproductive disorders. This information is ultimately required for the design of therapeutic options for patients with reproductive disorders including infertility.

该项目的总体目标是继续研究女性生殖的神经内分泌和性腺调节，重点关注 FSH、雌二醇和抑制素之间复杂的相互关系。 现在有证据表明雌二醇和抑制素都有助于女性 FSH 的负反馈控制。 然而，它们在正常月经周期的卵泡期和黄体期精确控制 FSH 中的相对作用尚未阐明。我们已经证明，在两种独特的情况下，雌二醇和抑制素的协调分泌发生了改变：在生殖衰老过程中，雌二醇水平在抑制素水平较低的情况下会增加，而在非洲裔美国女性中，正常生殖周期的特点是面对相同水平的抑制素，相对于白人女性，雌二醇增加。 确定这些变化的机制将为我们提供关于抑制素、雌二醇和促性腺激素在正常生殖生理学中相互作用的重要见解。 目标 1 将使用正常和 GnRH 缺乏的女性（其中雌激素分泌因芳香酶阻断而改变），确定雌二醇和抑制素对正常月经周期的卵泡期和黄体期 FSH 分泌负反馈调节的相对贡献。 目标 2 将通过研究固定 FSH 刺激反应中的抑制素和雌二醇分泌，并确定窦中颗粒细胞和抑制素亚基表达以及芳香酶功能和表达的数量，试图阐明生殖衰老过程中雌二醇和抑制素分泌之间二分法的机制。和排卵前卵泡作为生殖衰老的函数。 目标 3 将确定 FSH、雌二醇和抑制素之间的反馈和前馈相互作用，从而导致非裔美国女性正常生殖周期中雌二醇水平升高。 将使用雌激素输注方案检查反馈，而前馈将检查排卵前卵泡中雌二醇和抑制素分泌的控制。了解生殖系统下丘脑-垂体和卵巢组成部分的反馈和前馈动态对于了解生殖疾病的病理生理学至关重要。 这些信息最终是为患有生殖障碍（包括不孕症）的患者设计治疗方案所必需的。