胆固醇通过其在雄激素合成和 Hedgehog 信号通路中的发育作用促进雄性性别分化。
Cholesterol Contributes to Male Sex Differentiation Through Its Developmental Role in Androgen Synthesis and Hedgehog Signaling.
机构信息
Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53705, USA.
出版信息
Endocrinology. 2021 Jul 1;162(7). doi: 10.1210/endocr/bqab066.
Two specialized functions of cholesterol during fetal development include serving as a precursor to androgen synthesis and supporting hedgehog (HH) signaling activity. Androgens are produced by the testes to facilitate masculinization of the fetus. Recent evidence shows that intricate interactions between the HH and androgen signaling pathways are required for optimal male sex differentiation and defects of either can cause birth anomalies indicative of 46,XY male variations of sex development (VSD). Further, perturbations in cholesterol synthesis can cause developmental defects, including VSD, that phenocopy those caused by disrupted androgen or HH signaling, highlighting the functional role of cholesterol in promoting male sex differentiation. In this review, we focus on the role of cholesterol in systemic androgen and local HH signaling events during fetal masculinization and their collective contributions to pediatric VSD.
胆固醇在胎儿发育过程中有两个特殊功能，包括作为雄激素合成的前体和支持 Hedgehog（HH）信号活性。雄激素由睾丸产生，以促进胎儿的男性化。最近的证据表明，HH 和雄激素信号通路之间的复杂相互作用是最佳男性性别分化所必需的，而这两种通路的缺陷都会导致出生异常，表明存在 46,XY 男性性别发育变异（VSD）。此外，胆固醇合成的扰动会导致发育缺陷，包括 VSD，这些缺陷与雄激素或 HH 信号的破坏引起的缺陷类似，突出了胆固醇在促进男性性别分化中的功能作用。在这篇综述中，我们重点讨论胆固醇在胎儿男性化过程中系统雄激素和局部 HH 信号事件中的作用，以及它们对儿科 VSD 的共同贡献。
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