PMID: 18406239Apr 15, 2008Paper

The regulation of human P450c17 activity: relationship to premature adrenarche, insulin resistance and the polycystic ovary syndrome

Trends in Endocrinology and Metabolism : TEM
Richard J AuchusW L Miller

Abstract

The polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and insulin resistance, but the connection between these two features has been unclear. Androgen synthesis is regulated in part by the ratio of the 17alpha-hydroxylase and 17,20 lyase activities of P450c17. Three separate lines of evidence show that the ratio of lyase to hydroxylase activity is regulated by electron flow from P450 oxidoreductase. Lyase activity and androgen synthesis are particularly dependent on the serine phosphorylation of P450c17. Serine phosphorylation of the insulin receptor beta chain causes insulin resistance, and some PCOS women have hyperphosphorylated receptors. We hypothesize that an overactive serine/threonine kinase hyperphosphorylates both the insulin receptor and P450c17 in PCOS, accounting for the characteristic insulin resistance and hyperandrogenism of this disease.

References

Dec 1, 1979·The Journal of Clinical Endocrinology and Metabolism·G C LachelinS S Yen
Jan 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·B C ChungW L Miller
Aug 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·G E BollagD E Koshland
Oct 1, 1972·Clinical Endocrinology·M ZachmannA Prader
Sep 30, 1982·Biochemical and Biophysical Research Communications·M Onoda, P F Hall
Nov 7, 1995·Proceedings of the National Academy of Sciences of the United States of America·L H ZhangW L Miller
Jun 1, 1995·The Journal of Steroid Biochemistry and Molecular Biology·T Yanase
Mar 10, 1995·Archives of Biochemistry and Biophysics·M KatagiriM R Waterman
Jan 1, 1996·Methods in Enzymology·S E Graham-Lorence, J A Peterson
Aug 5, 1997·Proceedings of the National Academy of Sciences of the United States of America·M WangJ J Kim
Nov 5, 1997·Nature Genetics·D H GellerW L Miller
Mar 7, 1998·The Journal of Biological Chemistry·R J AuchusW L Miller

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Citations

Jul 9, 2002·Clinical Endocrinology·Taly MeasClaire Lévy-Marchal
Jan 8, 2000·Acta Paediatrica. Supplement·W L Miller
Dec 18, 1998·Journal of Endocrinological Investigation·V Toscano
Jan 17, 2012·Steroids·Sylvain BellangerJean-Patrice Baillargeon
Mar 28, 2007·Journal of Biotechnology·Norbert W KolarPieter Swart
Mar 16, 2016·The Journal of Steroid Biochemistry and Molecular Biology·Megh Raj BhattLisandra L Martin
Sep 13, 2016·Molecular and Cellular Endocrinology·Renate Louw-du ToitDonita Africander
Jan 15, 1999·Endocrine Research·W L MillerR J Auchus
Feb 24, 2001·Endocrine Research·R J AuchusW L Miller
May 24, 2011·The Journal of Clinical Endocrinology and Metabolism·Sharon E OberfieldAdrienne T Gerken
Mar 19, 2005·Endocrinology·Walter L Miller
Jun 18, 1999·The Journal of Clinical Endocrinology and Metabolism·T C LeeR J Auchus
Oct 27, 2015·World Journal of Gastroenterology : WJG·Laura Marino, François R Jornayvaz
Nov 18, 2021·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Jenifer Lizbet Hernández-JiménezNayeli Torres-Ramírez

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