Defects in Androgen Biosynthesis Causing 46,XY Disorders of Sexual Development
October 2012
in “
Seminars in reproductive medicine
”
androgen biosynthesis 46,XY disorders of sexual development DSD genetic defects androgen production androgen-dependent diseases lipoid congenital adrenal hyperplasia CAH P450 oxidoreductase deficiencies POR deficiencies steroidogenesis backdoor pathway dihydrotestosterone DHT paracrine factor male genital development male sexual differentiation 46,XY DSD lipoid CAH
TLDR Genetic defects in androgen production are linked to male developmental disorders and are improving treatment understanding.
The document discussed various genetic defects in the androgen biosynthesis pathway that cause 46,XY disorders of sexual development (DSD). It highlighted that each step in the classical androgen biosynthesis pathway could have at least one genetic defect, with some steps having multiple defects leading to similar disorders. The study of these genetic defects has advanced the understanding of the pathways, essential genes, and enzymatic steps necessary for androgen production, aiding in the development of better treatments for androgen-dependent diseases. Additionally, the discovery of nonclassical lipoid congenital adrenal hyperplasia (CAH) and P450 oxidoreductase (POR) deficiencies has broadened the spectrum of diseases caused by disordered steroidogenesis. The recognition of the backdoor pathway to dihydrotestosterone (DHT) has provided new insights into steroid flux in both normal and pathological states. The findings suggested that both the classic and backdoor pathways are essential for male genital development, with DHT acting as both a paracrine factor and a hormone, thus revising the understanding of male sexual differentiation mechanisms.
