OVARIAN FAILURE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。二聚体抑制素、激活素和卵泡抑素（FS）最初都被认为是调节卵泡刺激素（FSH）分泌的生殖内分泌激素。然而，这种模式在当前医学证据的重压下得到了扩展。激活素似乎在生殖和非生殖组织中起着中心的自分泌/旁分泌作用。抑制素和FS在激活素信号传导中都有重要的反调控作用。随着生殖衰老，抑制素B随着卵泡池的减少而下降，扰乱了育龄中期正常月经周期的动态。抑制素对卵泡刺激素分泌的抑制作用的丧失似乎是导致月经周期缩短和生育后期一些激素不可预测性的初始内分泌事件。它也可能与生育能力的下降有关，这种下降发生在生殖衰老过程中。在男性中，抑制素B是性腺能力的良好标志，抑制素B随年龄的下降反映了两性性腺储备的下降。循环激活随着年龄的增长而增加，但它对女性和男性生殖的影响尚不清楚。无论男性还是女性，FS似乎都不会随着年龄的增长而发生很大的变化。这种微妙平衡的调节三位一体中与年龄相关的波动影响生殖能力和时间衰老的后遗症。对这些激素作用的分子途径的阐明可能会使它们与目前在衰老中的概念作用更紧密地结合起来。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dimeric inhibins, activins, and follistatin (FS) were all initially characterized as reproductive endocrine hormones that regulate follicle-stimulating hormone (FSH) secretion. This model, however, has expanded under the weight of current medical evidence. Activin appears to play a central auto/paracrine role in reproductive and nonreproductive tissues. Inhibin and FS each have important counterregulatory functions in activin signaling. With reproductive aging, inhibin B declines along with the follicular pool and disturbs the dynamics of the normal menstrual cycle of midreproductive age. The loss of inhibin restraint of FSH secretion appears to be the initiating endocrine event that leads to menstrual cycle shortening and some of the hormonal unpredictability of the late reproductive years. It may also be related to the decline in fertility that occurs in reproductive aging. In men, inhibin B is an excellent marker for gonadal competence, and the decline of inhibin B with age reflects decreased gonadal reserve in both sexes. Circulating activin increases with aging, but its effect on reproduction in women and men is not clear. FS does not appear to change greatly with aging in men or women. The age-related fluctuations in this delicately balanced regulatory triad influence reproductive capacity and the sequelae of chronological aging. Elucidation of the molecular pathways responsible for the action of these hormones may allow closer integration with their current Conceptual roles in aging.