Inhibition of placental CYP19A1 activity remains as a valid hypothesis for 46,XX virilization in P450 oxidoreductase deficiency

Flück, Christa E.; Parween, Shaheena; Rojas Velazquez, Maria Natalia; Pandey, Amit Vikram (2020). Inhibition of placental CYP19A1 activity remains as a valid hypothesis for 46,XX virilization in P450 oxidoreductase deficiency. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 117(26), pp. 14632-14633. National Academy of Sciences NAS 10.1073/pnas.2003154117

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Cytochrome P450 oxidoreductase deficiency (PORD), caused by mutations in P450 oxidoreductase (POR), is a disorder of steroid metabolism often characterized by disordered sexual development (1⇓–3). POR is required for enzymatic activities of multiple cytochrome P450 enzymes (4). In PNAS, Reisch et al. (5) propose “alternative pathway androgen biosynthesis” as the cause of 46,XX virilization in PORD. We are pleased to see the expansion of the role of alternative pathway in sexual development previously demonstrated by us in 46,XY individuals (6), but have some concerns regarding the assumption that virilization of 46,XX individuals in PORD is mainly via an alternative pathway. The choice of steroid analysis by Reisch et al. (5) from only 46,XY individuals to propose a hypothesis for 46,XX virilization is baffling. Another recent study found low to undetectable levels of 17-hydroxy-dihydroprogesterone, 17-hydroxy-allopregnanolone, and androsterone, the steroids in alternative pathway produced via CYP17A1, in the 46,XX fetal adrenals and attributed it to a lack of SRD5A1 expression in fetal adrenal (7). We have previously reported that mutations in the key enzymes of the alternative pathway cause 46,XY undervirilization (6). By contrast, mutations in aromatase (CYP19A1) cause genital virilization in 46,XX individuals (8), which prompted us to reexamine the results of Reisch et al. (5).

Item Type:

Journal Article (Further Contribution)


04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Endocrinology/Metabolic Disorders

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Flück Pandey, Christa Emma, Parween, Shaheena, Rojas Velazquez, Maria Natalia, Pandey, Amit Vikram


600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology




National Academy of Sciences NAS


[4] Swiss National Science Foundation ; [UNSPECIFIED] Novartis foundation for medical biological research




Amit Vikram Pandey

Date Deposited:

25 Jun 2020 12:05

Last Modified:

06 Jan 2023 18:33

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