alexa Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes.
Psychiatry

Psychiatry

Journal of Addiction Research & Therapy

Author(s): Yamazaki H, Shimada T

Abstract Share this page

Abstract Roles of human cytochrome P450 (P450 or CYP) 2C9, 2C19, and 3A4 in the oxidation of progesterone and testosterone were studied in recombinant P450 enzymes and in human liver microsomes. In vitro inhibition experiments showed that progesterone and its 17alpha- and 21-hydroxylated metabolites and 11-deoxycortisol suppressed the CYP2C19-dependent R-warfarin 7-hydroxylation activities, with progesterone being the most active. These steroid chemicals also inhibited CYP2C9-dependent S-warfarin 7-hydroxylation activities though lesser extents seen with those in CYP2C19 enzyme. Progesterone was found to be a competitive inhibitor of CYP2C19 and CYP2C9 in human liver microsomes. Recombinant CYP2C19 catalyzed progesterone to form 21-hydroxyprogesterone as a major product and 16alpha- and 17alpha-hydroxyprogesterone as minor products. CYP2C9 also had progesterone 21-hydroxylation activities, although the activities were lower than those catalyzed by CYP2C19. Vmax/Km ratios for the progesterone 21-hydroxylation activity of CYP2C19 were determined to be 13- and 32-fold higher than those of CYP2C9 and 3A4, respectively. CYP3A4 oxidized progesterone to form 16alpha-, 6beta-, and 2beta-hydroxyprogesterone as major products and 21-hydroxyprogesterone as a minor product, but did not produce detectable levels of 17alpha-hydroxyprogesterone. Immunoinhibition experiments suggested that anti-CYP2C9 (which inhibits both CYP2C9 and CYP2C19 catalytic activities) suppressed the progesterone 21-hydroxylation activities catalyzed by liver microsomes of humans and monkeys and that anti-CYP2C11 inhibited the progesterone 21-hydroxylation activities catalyzed by liver microsomes of male rats. CYP2C19 was also found to oxidize testosterone at 17-position to form androstenedione. Androstenedione formation catalyzed by liver microsomes of humans and monkeys and of male rats was suppressed by anti-CYP2C9 and anti-CYP2C11, respectively. These results suggest that CYP2C19 plays important roles in the oxidation of progesterone and testosterone in human liver microsomes, although the physiological significance of these metabolic pathways remains unclear. CYP2C9 may have some, but lesser extent than those by CYP2C19, of the catalytic roles for the metabolism of progesterone and testosterone by human liver microsomes. This article was published in Arch Biochem Biophys and referenced in Journal of Addiction Research & Therapy

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords