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Titolo:
Differential activity of the cytochrome P450 17 alpha-hydroxylase and steroidogenic acute regulatory protein gene promoters in normal and polycystic ovary syndrome theca cells
Autore:
Wickenheisser, JK; Quinn, PG; Nelson, VL; Legro, RS; Strauss, JF; McAllister, JM;
Indirizzi:
Penn State Univ, Milton S Hershey Med Ctr, Dept Cellular & Mol Physiol, Coll Med, Hershey, PA 17033 USA Penn State Univ Hershey PA USA 17033 iol, Coll Med, Hershey, PA 17033 USA Penn State Univ, Dept Obstet & Gynecol, Coll Med, Hershey, PA 17033 USA Penn State Univ Hershey PA USA 17033 col, Coll Med, Hershey, PA 17033 USA Univ Penn, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 mens Hlth, Philadelphia, PA 19104 USA
Titolo Testata:
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
fascicolo: 6, volume: 85, anno: 2000,
pagine: 2304 - 2311
SICI:
0021-972X(200006)85:6<2304:DAOTCP>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
FOLLICLE-STIMULATING-HORMONE; SIDE-CHAIN CLEAVAGE; GRANULOSA-CELLS; TRANSCRIPTIONAL REGULATION; RECEPTOR SUPERFAMILY; AD4-BINDING PROTEIN; BOVINE CYP17; STAR GENE; EXPRESSION; CAMP;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: McAllister, JM Penn State Univ, Milton S Hershey Med Ctr, Dept Cellular & Mol Physiol, Coll Med, 500 Univ Dr, Hershey, PA 17033 USA Penn State Univ 500 Univ Dr Hershey PA USA 17033 17033 USA
Citazione:
J.K. Wickenheisser et al., "Differential activity of the cytochrome P450 17 alpha-hydroxylase and steroidogenic acute regulatory protein gene promoters in normal and polycystic ovary syndrome theca cells", J CLIN END, 85(6), 2000, pp. 2304-2311

Abstract

17 alpha-Hydroxylase (CYP17) expression in propagated theca cells isolatedfrom the ovaries of women with polycystic ovary syndrome (PCOS) is persistently elevated, compared with theca cells isolated from normal ovaries. To investigate the mechanism for increased CYP17 messenger RNA accumulation inPCOS theca cells, we examined CYP17 and steroidogenic acute regulatory protein (StAR) promoter activities in normal and PCOS theca cells. Conditions were established to transiently transfect human theca cells with reporter gene constructs containing 5' truncations of the human CYP17 and StAR promoters. Cotransfection of a steroidogenic factor-1 expression plasmid was found to be required for detection of basal and forskolin-stimulated CYP17 promoter activity but not for StAR promoter activity. However, cotransfection with a steroidogenic factor-1 expression plasmid augmented both basal and forskolin-stimulated StAR promoter activity. CYP17 reporter activity was compared in theca cells isolated from normal and PCOS patients. Basal and forskolin stimulated CYP17 promoter activity was 4-fold greater in PCOS cells than in theca cells isolated from normal ovaries. In contrast, StAR promoter activity, and the activity of a reporter construct containing three copies of a cAMP response element (3xCRE), were similar in normal and PCOS theca cells. The results of these studies document: 1) that basal and cAMP-dependent CYP17 gene transcription is increased in PCOS theca cells; 2) that thereis differential regulation of promoters of genes required for steroidogenesis in PCOS theca cells; and 3) that passaged normal and PCOS theca cells provide a model system for studying tissue-specific regulation of genes encoding steroidogenic enzymes and identifying the molecular mechanisms involved in increased androgen production in PCOS.

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Documento generato il 23/09/20 alle ore 14:51:21