期刊
ENDOCRINOLOGY
卷 162, 期 7, 页码 -出版社
ENDOCRINE SOC
DOI: 10.1210/endocr/bqab066
关键词
cholesterol; male sex differentiation; androgen; disorders of cholesterol synthesis; hedgehog signaling; disorders of sex development
资金
- National Institutes of Health [R01HD090660]
This article discusses the crucial role of cholesterol during fetal masculinization, particularly in androgen synthesis and HH signaling activity, emphasizing its functional importance in promoting male sex differentiation. Perturbations in cholesterol synthesis may lead to developmental defects such as VSD, similar to those caused by disrupted androgen or HH signaling pathways.
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.
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