Transgenic overexpression of plasminogen activator inhibitor-1 promotes the development of polycystic ovarian changes in female mice.

Transgenic overexpression of plasminogen activator inhibitor-1 promotes the development of polycystic ovarian changes in female mice. Research Abstract Details 

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Transgenic overexpression of plasminogen activator inhibitor-1 promotes the development of polycystic ovarian changes in female mice. Abstract Text:

Jessica K Devin,Joyce E Johnson,Mesut Eren,Linda A Gleaves,William S Bradham,John R Bloodworth,Douglas E Vaughan,

Reproductive age women (5-10%) are affected by the polycystic ovarian syndrome (PCOS), a diagnosis which confers lifelong cardiovascular and reproductive health implications. Plasminogen activator inhibitor-1 (PAI-1), the main physiological inhibitor of plasminogen activation, is consistently elevated in women with PCOS, regardless of metabolic status. Interestingly, the plasminogen system has long been implicated in proteolytic processes within the dynamic ovary. A non-physiologic elevation in PAI-1 may thus contribute systemically to endothelial dysfunction and locally to abnormal ovarian phenotype and function. We herein characterize the phenotypic alterations in ovaries from transgenic mice, which constitutively express a stable form of human PAI-1 and determine the plasma testosterone level in these mice as opposed to their unaffected counterparts. Over half of the ovaries from transgenic mice were found to contain large cystic structures, in contrast to wild-type controls of the same genetic background (53% (N = 17) vs 5% (N = 22); P = 0.001). Plasma testosterone was nearly twofold elevated in transgenic female mice versus wild-type females (0.312 ng/ml +/- 0.154 (N = 10) vs 0.181 ng/ml +/- 0.083 (N = 8); P = 0.014). An elevation in PAI-1 therefore appears to predispose mice to the development of this abnormal architecture, which in turn is associated with an increase in plasma testosterone. Therefore, we propose that an inappropriate elevation in PAI-1 contributes to the development of polycystic structures; these findings may thus reorient the efforts aimed at the development of therapeutic agents for the treatment of this increasingly common syndrome.

Transgenic overexpression of plasminogen activator inhibitor-1 promotes the development of polycystic ovarian changes in female mice. Publishing Authors By Initials

JK Devin,JE Johnson,M Eren,LA Gleaves,WS Bradham,JR Bloodworth,DE Vaughan,

For similar polycyclic compounds: steroids: androstanes: androstenes: androstenols: testosterone research abstracts see: polycyclic compounds: steroids: androstanes: androstenes: androstenols: testosterone research

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Transgenic overexpression of plasminogen activator inhibitor-1 promotes the development of polycystic ovarian changes in female mice. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of molecular endocrinology

VOLUME: 39

Page Numbers: 9-16

Journal Abbreviation: J. Mol. Endocrinol.

ISSN: 1479-6813

DAY: 3

MONTH: Jul

YEAR: 2007

Transgenic overexpression of plasminogen activator inhibitor-1 promotes the development of polycystic ovarian changes in female mice. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8902617

Transgenic overexpression of plasminogen activator inhibitor-1 promotes the development of polycystic ovarian changes in female mice. Keywords Mesh Terms:

KEYWORDS: Testosterone

MESH TERMS: blood

Chemical & Substance for Abstract: Transgenic overexpression of plasminogen activator inhibitor-1 promotes the development of polycystic ovarian changes in female mice. Information

Substance Name: Testosterone

Registry Number: 58-22-0

Grant and Affiliation Information for Transgenic overexpression of plasminogen activator inhibitor-1 promotes the development of polycystic ovarian changes in female mice.

AFFILIATION: Division of Cardiovascular Medicine, 354 Preston Research Building, Vanderbilt University School of Medicine, 2220 Pierce Avenue, Nashville, Tennessee 37232, USA.

Country: England

AGENCY: United States NHLBI

GRANT: P50HL081009

ACRONYM: HL

MEDLINETA: J Mol Endocrinol

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