激活素在人卵巢中的生理作用

Hsun‐Ming Chang, P. Leung
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引用次数: 8

摘要

激活素最初作为促卵泡激素的刺激物在垂体中被发现,是抑制素亚基的同二聚体或异二聚体,属于转化生长因子-&bgr;总科。随后的研究表明,这些生长因子在调节包括卵巢在内的多个器官的各种功能方面发挥着多方面的作用。抑制素亚基(&agr; &bgr;A, &bgr;B, &bgr;C)及其同源受体和激活素结合蛋白(抑制素和卵泡抑素)在人类卵巢生长卵泡主要细胞中的时空表达表明,这些激活素亚型参与卵巢生物学。从动物研究和临床样本收集的信息表明,这些局部产生的生长因子是各种卵巢功能的关键调节剂,包括原始生殖细胞发育、卵泡生长发育、卵巢类固醇生成、细胞外基质重塑、卵母细胞成熟、排卵和黄体功能。与促性腺激素一起,卵泡内激活素对生长中的卵泡发挥协同和互补作用,帮助它们发育成熟、有能力的卵母细胞,为受精做准备。激活素异常表达、激活素/卵泡抑制素比例失衡以及激活素信号通路失调在生殖衰老、多囊卵巢综合征和卵巢癌等多种卵巢病理中均有发现。最近我们对激活素和相关卵巢异常发展的分子相互作用和机制的理解取得了进展,这为疾病的发病机制提供了新的见解,并增加了实现有效和安全治疗的机会。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Physiological roles of activins in the human ovary
Abstract Initially discovered in the pituitary as stimulators of follicle stimulating hormone, activins are homo- or heterodimers of inhibin subunits, which belong to the transforming growth factor-&bgr; superfamily. Subsequent studies have demonstrated that these growth factors play multifaceted roles in regulating various functions in multiple organs, including the ovary. The spatial and temporal expression of inhibin subunits (&agr;, &bgr;A, &bgr;B, and &bgr;C), their cognate receptors, and activin-binding proteins (inhibins and follistatins) in the principal cells of growing follicles in human ovaries indicates that these activin isoforms are involved in ovarian biology. Information collected from animal studies and clinical samples suggests that these locally produced growth factors are crucial modulators of various ovarian functions, including primordial germ cell development, follicular growth and development, ovarian steroidogenesis, extracellular matrix remodeling, oocyte maturation, ovulation, and luteal function. Along with gonadotropins, intrafollicular activins exert synergistic and complementary effects on growing follicles to help them develop a mature, competent oocyte that is prepared for fertilization. Abnormal activin expression, an imbalanced activin/follistatin ratio, and the dysregulation of the activin signaling pathway have been observed in several ovarian pathologies, such as reproductive aging, polycystic ovary syndrome, and ovarian cancers. Recent advancements in our understanding of the molecular interactions and mechanisms that underlie activins and the development of related ovarian abnormalities have provided insights into disease pathogenesis and increased opportunities to achieve efficient and safe therapies.
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