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

被引：32

作者：

Auchus, RJ ^{[1
]}

Geller, DH ^{[1
]}

Lee, TC ^{[1
]}

Miller, WL ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA

来源：

TRENDS IN ENDOCRINOLOGY AND METABOLISM | 1998年 / 9卷 / 02期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/S1043-2760(98)00016-2

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 17 alpha-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. Serene 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.

引用

页码：47 / 50

页数：4

共 30 条

[1] Cytochrome b5 augments the 17,20-lyase activity of human P450c17 without direct electron transfer [J].

Auchus, RJ ;

Lee, TC ;

Miller, WL .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (06) :3158-3165

[2] PROTEIN-KINASE-C DIRECTLY PHOSPHORYLATES THE INSULIN-RECEPTOR INVITRO AND REDUCES ITS PROTEIN-TYROSINE KINASE-ACTIVITY [J].

BOLLAG, GE ;

ROTH, RA ;

BEAUDOIN, J ;

MOCHLYROSEN, D ;

KOSHLAND, DE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (16) :5822-5824

[3] EVIDENCE FOR A SINGLE GENE EFFECT CAUSING POLYCYSTIC OVARIES AND MALE PATTERN BALDNESS [J].

CAREY, AH ;

CHAN, KL ;

SHORT, F ;

WHITE, D ;

WILLIAMSON, R ;

FRANKS, S .

CLINICAL ENDOCRINOLOGY, 1993, 38 (06) :653-658

[4] CYTOCHROME P450C17 (STEROID 17-ALPHA-HYDROXYLASE/17,20 LYASE) - CLONING OF HUMAN ADRENAL AND TESTIS CDNAS INDICATES THE SAME GENE IS EXPRESSED IN BOTH TISSUES [J].

CHUNG, BC ;

PICADOLEONARD, J ;

HANIU, M ;

BIENKOWSKI, M ;

HALL, PF ;

SHIVELY, JE ;

MILLER, WL .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (02) :407-411

[5] EXCESSIVE INSULIN-RECEPTOR SERINE PHOSPHORYLATION IN CULTURED FIBROBLASTS AND IN SKELETAL-MUSCLE - A POTENTIAL MECHANISM FOR INSULIN-RESISTANCE IN THE POLYCYSTIC-OVARY-SYNDROME [J].

DUNAIF, A ;

XIA, JR ;

BOOK, CB ;

SCHENKER, E ;

TANG, ZC .

JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (02) :801-810

[6] The genetic and functional basis of isolated 17,20-lyase deficiency [J].

Geller, DH ;

Auchus, RJ ;

Mendonca, BB ;

Miller, WL .

NATURE GENETICS, 1997, 17 (02) :201-205

[7] Structural alignments of P450s and extrapolations to the unknown [J].

GrahamLorence, SE ;

Peterson, JA .

CYTOCHROME P450, PT B, 1996, 272 :315-326

[8] POSTPUBERTAL OUTCOME IN GIRLS DIAGNOSED OF PREMATURE PUBARCHE DURING CHILDHOOD - INCREASED FREQUENCY OF FUNCTIONAL OVARIAN HYPERANDROGENISM [J].

IBANEZ, L ;

POTAU, N ;

VIRDIS, R ;

ZAMPOLLI, M ;

TERZI, C ;

GUSSINYE, M ;

CARRASCOSA, A ;

VICENSCALVET, E .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1993, 76 (06) :1599-1603

[9] INSULIN ACTION, DIABETOGENES, AND THE CAUSE OF TYPE-II DIABETES [J].

KAHN, CR .

DIABETES, 1994, 43 (08) :1066-1084

[10] THE ROLE OF CYTOCHROME B(5) IN THE BIOSYNTHESIS OF ANDROGENS BY HUMAN P450C17 [J].

KATAGIRI, M ;

KAGAWA, N ;

WATERMAN, MR .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1995, 317 (02) :343-347

← 1 2 3 →