Cholesterol contributes to male sex differentiation through its developmental role in androgen synthesis and hedgehog signaling.
Cholesterol contributes to male sex differentiation through its developmental role in androgen synthesis and hedgehog signaling.
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DOI：
10.1210/endocr/bqab066
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发表时间：
2021-03
期刊：
影响因子：
4.8
通讯作者：
Anbarasi Kothandapani;C. Jefcoate;Joan S. Jorgensen
中科院分区：
文献类型：
--
作者：
Anbarasi Kothandapani;C. Jefcoate;Joan S. Jorgensen
胆固醇在胎儿发育期间的两个专门功能包括作为雄激素合成的前体和支持hedgehog（HH）信号传导活性。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和雄激素信号传导途径之间的复杂相互作用是最佳男性性别分化所必需的，任何一种的缺陷都可能导致出生异常，表明46，XY男性性发育变异（VSD）。此外，胆固醇合成中的扰动可导致发育缺陷，包括VSD，其表型复制由破坏的雄激素或HH信号传导引起的发育缺陷，突出了胆固醇在促进雄性性别分化中的功能作用。在这篇综述中，我们重点关注胆固醇在胎儿男性化过程中全身雄激素和局部HH信号事件中的作用及其对儿童VSD的共同贡献。
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.