Growth Differentiation Factor 9 Promotes Rat Preantral Follicle Growth by Up-Regulating Follicular Androgen Biosynthesis
Growth Differentiation Factor 9 Promotes Rat Preantral Follicle Growth by Up-Regulating Follicular Androgen Biosynthesis
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DOI：
10.1210/en.2008-1536
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发表时间：
2009-06-01
期刊：
影响因子：
4.8
通讯作者：
Tsang, Benjamin K.
中科院分区：
文献类型：
--
作者：
Orisaka, Makoto;Jiang, Jin-Yi;Tsang, Benjamin K.
从腔前到腔早期，从促性腺激素依赖性和卵泡命运来看，是卵泡发育的倒数第二阶段。尽管卵母细胞-体细胞通讯在早期卵泡发育中很重要，但我们对卵母细胞衍生的生长分化因子-9在腔前卵泡发育过程中的确切作用的了解还不完全。我们通过体外基因操作(即在卵母细胞内注射GDF-9反义寡核苷酸)和腔前卵泡培养相结合的方法，研究了卵母细胞来源的GDF-9在腔前到腔前早期的卵泡发育和类固醇生成过程中是否以及以何种方式控制。卵母细胞内注射反义GDF-9抑制了大鼠腔前卵泡的体外生长，而GDF-9促进了卵泡的发育。GDF-9促进腔前卵泡睾酮的产生。GDF-9反义抑制培养的卵泡中雄激素的产生和CYP17A1的mRNA表达，这种反应被外源GDF-9减弱。非芳香化雄激素5α-二氢睾酮挽救了GDF-9下调引起的卵泡生长停滞。雄激素受体特异性拮抗剂氟他胺可抑制GDF-9诱导的腔前卵泡生长。结果提示，GDF-9通过上调卵泡雄激素的生物合成，在促进腔前卵泡生长中发挥重要作用。从腔前到腔早期的卵泡发育过程中，GDF-9对细胞色素P17A1的表达是必不可少的。(内分泌学150：2740-2748,2009)
The transition from preantral to early antral stage is the penultimate stage of ovarian follicular development in terms of gonadotropin dependence and follicle destiny. Although oocyte-somatic cell communication is important in early follicular development, our knowledge of the precise role of the oocyte-derived growth differentiation factor (GDF)-9 during preantral follicle growth is incomplete. We examined whether and by what means oocyte-derived GDF-9 controls follicular development and steroidogenesis during the preantral to early antral transition, by a combination of in vitro gene manipulation (i.e. intraoocyte injection of GDF-9 antisense oligos) and preantral follicle culture. Intraoocyte injection of GDF-9 antisense suppressed rat preantral follicle growth in vitro, whereas GDF-9 enhanced follicular development. GDF-9 augmented testosterone production in preantral follicles. GDF-9 antisense suppressed androgen production and CYP17A1 mRNA expression in cultured follicles, a response attenuated by exogenous GDF-9. The nonaromatizable androgen 5 alpha-dihydrotestosterone rescued the follicular growth arrest caused by GDF-9 down-regulation. The specific androgen receptor antagonist flutamide suppressed GDF-9-induced preantral follicle growth in vitro. The data suggest that GDF-9 plays an important role in promoting preantral follicle growth by up-regulating follicular androgen biosynthesis. GDF-9 is essential for CYP17A1 expression during follicular development from the preantral to the early antral stage. (Endocrinology 150: 2740-2748, 2009)