Reproductive Biology Unit and Division of Reproductive Medicine, Department of Obstetrics and Gynecology and Cellular and Molecular Medicine, University of Ottawa, Ottawa Hospital Research Institute, The Ottawa Hospital (Civic Campus), Ottawa, Ontario, Canada.
Endocrinology. 2009 Dec;150(12):5566-74. doi: 10.1210/en.2009-0262. Epub 2009 Oct 15.
FSH regulates follicular growth in a stage-development fashion. Although preantral follicle stage is gonadotropin responsive, FSH is not required for preantral follicular growth. With the antrum, the follicles continue growing under the influence of FSH and become gonadotropin dependent. Although thyroid hormone is important for normal female reproductive function, its role and interaction with FSH in the regulation of preantral ovarian follicular growth is yet to be defined. In the present study, we have examined the action and interaction of FSH and T(3) in the regulation of the growth of preantral follicles, especially in their transition from preantral to early antral stage, using an established follicle culture system and evaluated the involvement of growth differentiation factor-9 (GDF-9) in this process in vitro. We have demonstrated that although T(3) alone had no effect on follicular development, it markedly enhanced FSH-induced preantral follicular growth. Although FSH alone significantly down-regulated FSH receptor (FSHR) mRNA abundance in the preantral follicles and T(3) alone was ineffective, expression of the message was significantly increased in the presence of both hormones. In addition, intra-oocyte injection of GDF-9 antisense oligonucleotides (GDF-9 morpholino) induced follicular cell apoptosis and suppressed follicular growth induced by FSH and T(3). These responses were attenuated by exogenous GDF-9. Our findings support the concept that thyroid hormone regulates ovarian follicular development through its direct action on the ovary and that promotes FSH-induced preantral follicular growth through up-regulation of FSHR, a mechanism dependent on the expression and action of oocyte-derived GDF-9.
FSH 以阶段发育的方式调节卵泡生长。虽然窦前卵泡阶段对促性腺激素有反应，但 FSH 不是窦前卵泡生长所必需的。随着窦腔的形成，卵泡在 FSH 的影响下继续生长，并变得依赖促性腺激素。虽然甲状腺激素对女性正常生殖功能很重要，但它在调节窦前卵巢卵泡生长中的作用及其与 FSH 的相互作用尚未确定。在本研究中，我们使用已建立的卵泡培养系统，研究了 FSH 和 T(3)在调节窦前卵泡生长中的作用和相互作用，特别是在其从窦前到早期窦状期的过渡中，并评估了生长分化因子-9 (GDF-9) 在这个过程中的体外作用。我们已经证明，虽然 T(3) 单独作用对卵泡发育没有影响，但它显著增强了 FSH 诱导的窦前卵泡生长。虽然 FSH 单独显著下调了窦前卵泡中 FSH 受体 (FSHR) mRNA 的丰度，而 T(3) 单独作用无效，但在两种激素存在的情况下，表达明显增加。此外，卵内注射 GDF-9 反义寡核苷酸 (GDF-9 吗啉代) 可诱导卵泡细胞凋亡，并抑制 FSH 和 T(3) 诱导的卵泡生长。这种反应可以被外源性 GDF-9 减弱。我们的研究结果支持这样的概念，即甲状腺激素通过其对卵巢的直接作用调节卵巢卵泡发育，并通过上调 FSHR 促进 FSH 诱导的窦前卵泡生长，这一机制依赖于卵源性 GDF-9 的表达和作用。
