Role of CYP27A1 in progesterone metabolism in vitro and in vivo

G. Escher, I. Vogeli, R. Escher, Robert Tuckey, S. Erickson, Z. Krozowski, F.J. Frey

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


In the kidney, progesterone is inactivated to 20α-dihydro-progesterone (20α-DH-progesterone) to protect the mineralocorticoid receptor from progesterone excess. In an attempt to clone the enzyme with 20α-hydroxysteroid activity using expression cloning in CHOP cells and a human kidney expression library, serendipitously cDNA encoding CYP27A1 was isolated. Overexpression of CYP27A1 in CHOP cells decreased progesterone conversion to 20α-DH-progesterone in a dose-dependent manner, an effect enhanced by cotransfection with adrenodoxin and adrenodoxin reductase. Incubation of CHOP cells with 27-hydroxycholesterol, a product of CYP27A1, increased the ratio of progesterone to 20α-DH-progesterone in a concentration-dependent manner, indicating that the effect of CYP27A1 overexpression was mediated by 27-hydroxycholesterol. To analyze whether these observations are relevant in vivo, progesterone and 20α-DH-progesterone were measured by gas chromatography-mass spectometry in 24-h urine of CYP27A1 gene knockout (ko) mice and their control wild-type and heterozygote littermates. In CYP27A1 ko mice, urinary progesterone concentrations were decreased, 20α-DH-progesterone increased, and the progesterone-to-20α-DH-progesterone ratio decreased threefold (P <0.001). Thus CYP27A1 modulates progesterone concentrations. The underlying mechanism is inhibition of 20α-hydroxysteroid dehydrogenase by 27-hydroxycholesterol.
Original languageEnglish
Pages (from-to)E949-E955
JournalAmerican journal of physiology : endocrinology and metabolism
Issue number4
Publication statusPublished - 2009


Dive into the research topics of 'Role of CYP27A1 in progesterone metabolism in vitro and in vivo'. Together they form a unique fingerprint.

Cite this