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Glucocorticoid receptor-mediated regulation of MMP9 gene expression in human ovarian surface epithelial cells.
Rae, Michael T; Price, Deborah; Harlow, Christopher R; Critchley, Hilary O D; Hillier, Stephen G.
Afiliação
  • Rae MT; Centre for Reproductive Biology, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom.
Fertil Steril ; 92(2): 703-8, 2009 Aug.
Article em En | MEDLINE | ID: mdl-18722610
OBJECTIVE: To obtain proof-of-concept that locally produced anti-inflammatory steroids suppress ovulation-associated extracellular matrix proteases in human ovarian surface epithelial (OSE) cells. DESIGN: Primary OSE cell cultures treated with interleukin-1alpha (IL-1alpha) (500 pg/mL) as proxy for inflammation, with/without anti-inflammatory steroid (cortisol or progesterone [P], 0.01-1.0 microM). SETTING: Academic medical center. PATIENT(S): Sixteen premenopausal women (29-46 years) undergoing surgery for nonmalignant gynecological conditions. MAIN OUTCOME MEASURE(S): Semiquantitative extracellular matrix protease gene expression profiling with verification by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and gelatinase zymography. RESULT(S): Treatment with IL-1alpha stimulated messenger RNA (mRNA) expression of several ovulation-associated matrix metalloproteinase genes by OSE cell cultures, including gelatinase B (MMP9) but not gelatinase A (MMP2). The IL-1alpha-stimulated MMP9 mRNA production was suppressed by cortisol but not P. Cortisol but not P also dose-dependently suppressed IL-1alpha-stimulated MMP9 gelatinase activity and this effect was blocked by the glucocorticoid receptor antagonist RU486. CONCLUSION(S): In human OSE cells, stimulation of MMP9 gene expression and proteolytic activity by IL-1alpha is suppressed by anti-inflammatory cortisol through a glucocorticoid receptor-mediated mechanism. Because IL-1alpha also generates cortisol formation in OSE by stimulating cortisone reductase activity, these results support a role for intracrine cortisol in minimizing proteolytic damage to the OSE at ovulation.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ovário / Receptores de Glucocorticoides / Regulação Enzimológica da Expressão Gênica / Metaloproteinase 9 da Matriz / Células Epiteliais Limite: Adult / Female / Humans / Middle aged Idioma: En Revista: Fertil Steril Ano de publicação: 2009 Tipo de documento: Article País de afiliação: Reino Unido País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ovário / Receptores de Glucocorticoides / Regulação Enzimológica da Expressão Gênica / Metaloproteinase 9 da Matriz / Células Epiteliais Limite: Adult / Female / Humans / Middle aged Idioma: En Revista: Fertil Steril Ano de publicação: 2009 Tipo de documento: Article País de afiliação: Reino Unido País de publicação: Estados Unidos