State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, P.R. China.
Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury Repair, Zhengzhou, Henan, P.R. China.
Biol Reprod. 2019 Oct 25;101(4):760-770. doi: 10.1093/biolre/ioz132.
In recent studies, luteinizing hormone (LH) was reported to play important roles in oocyte maturation. However, the mechanism by which LH signaling, especially regarding the steroidogenesis process, affects oocyte maturation has not been clarified. In this study, zebrafish models with a functional deficiency in luteinizing hormone beta (Lhb) or steroidogenic acute regulatory protein (Star), an enzyme that promotes the transport of cholesterol into the inner mitochondrial membrane for maturation-induced hormone (MIH) production, were generated using transcription activator-like effector nucleases (TALENs). Similar phenotypes of the maturation-arrested oocytes in both female mutants have been observed. The levels of MIH in the oocytes of the female mutants were clearly decreased in both the lhb and star knockout zebrafish. The expression of star was dramatically down-regulated in the lhb mutant follicles and was clearly promoted by forskolin and hCG in vitro. Furthermore, treatment with the MIH precursors, pregnenolone or progesterone, as well as with MIH itself rescued the maturation-arrested oocyte phenotypes in both lhb and star mutants. The plasma levels of other steroids, including testosterone, estradiol, and cortisol, were not affected in the lhb mutants, while the levels of gonad hormones testosterone and estradiol were significantly increased in the star mutants. The cortisol levels were decreased in the star mutants. Collectively, our results confirm that LH plays important roles in the initiation of MIH synthesis from cholesterol and maintains oocyte maturation in zebrafish, as well as provide evidence that Star might act downstream of LH signaling in steroidogenesis.
在最近的研究中，黄体生成素（LH）被报道在卵母细胞成熟中发挥重要作用。然而，LH 信号转导（尤其是类固醇生成过程）如何影响卵母细胞成熟的机制尚未阐明。在这项研究中，使用转录激活因子样效应物核酸酶（TALENs）生成了黄体生成素β（Lhb）或类固醇急性调节蛋白（Star）功能缺陷的斑马鱼模型，Star 是一种促进胆固醇转运到线粒体内膜以产生成熟诱导激素（MIH）的酶。在这两种雌性突变体中都观察到成熟阻滞卵母细胞的相似表型。在 lhb 和 star 敲除斑马鱼中，卵母细胞中的 MIH 水平明显降低。lhb 突变滤泡中的 star 表达明显下调，并且在体外明显被 forskolin 和 hCG 促进。此外，用 MIH 前体孕烯醇酮或孕酮以及 MIH 本身处理可挽救 lhb 和 star 突变体中的成熟阻滞卵母细胞表型。lhb 突变体中的其他类固醇（包括睾酮、雌二醇和皮质醇）的血浆水平不受影响，而 star 突变体中的促性腺激素睾酮和雌二醇水平显著增加。star 突变体中的皮质醇水平降低。总之，我们的结果证实 LH 在胆固醇合成 MIH 的起始中发挥重要作用，并维持斑马鱼的卵母细胞成熟，并且提供了 Star 可能在类固醇生成中作为 LH 信号下游的证据。
