Increased expression of CYP1A1 and CYP1B1 in ovarian/peritoneal endometriotic lesions

Carla A Piccinato, Carla de Azevedo Piccinato, Rosa M Neme, Rosa Maria Neme, Natália Torres, Lívia Renta Sanches, Priscilla Bento Mattos Cruz Derogis, Priscilla Bento Matos Cruz Derogis, H.F. Brudniewski, Heloísa F Brudniewski, Júlio C. Rosa e Silva, Rui Alberto Ferriani, Rui A Ferriani
Reproduction (Cambridge, England) · 2016 · vol. 151(6) , pp. 683–692 · doi:10.1530/rep-15-0581 · PMID:27012269 · W2302857844
article OA: bronze CC0 ⤵ 20 in-corpus citations
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This study found increased CYP1A1 and CYP1B1 mRNA expression in superficial endometriotic lesions and ovarian stromal cells, correlating with slower estradiol metabolism in the latter.

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Abstract

Endometriosis is an estrogen-dependent disease affecting up to 10% of all premenopausal women. There is evidence that different endometriosis sites show distinct local estrogen concentration, which, in turn, might be due to a unique local estrogen metabolism. We aimed to investigate whether there was a site-specific regulation of selected enzymes responsible for the oxidative metabolism of estrogens in biopsy samples and endometrial and endometriotic stromal cells. Cytochrome P450 (CYP) 1A1 and CYP1B1 mRNA and protein expressions in deep-infiltrating (rectal, retossigmoidal, and uterossacral) lesions, superficial (ovarian and peritoneal) lesions, and eutopic and healthy (control) endometrium were evaluated by real-time PCR and western blot. Using a cross-sectional study design with 58 premenopausal women who were not under hormonal treatment, we were able to identify an overall increased CYP1A1 and CYP1B1 mRNA expression in superficial lesions compared with the healthy endometrium. CYP1A1 mRNA expression in superficial lesions was also greater than in the eutopic endometrium. Interestingly, we found a similar pattern of CYP1A1 and CYP1B1 expression in in vitro stromal cells isolated from ovarian lesions (n=3) when compared with stromal cells isolated from either rectum lesions or eutopic endometrium. In contradiction, there was an increased half-life of estradiol (measured by HPLC-MS-MS) in ovarian endometriotic stromal cells compared with paired eutopic stromal endometrial cells. Our results indicate that there is a site-dependent regulation of CYP1A1 and CYP1B1 in ovarian/peritoneal lesions and ovarian endometriotic stromal cells, whereas a slower metabolism is taking place in these cells.

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Condition tags

endometriosis

MeSH descriptors

Cytochrome P-450 CYP1A1 Cytochrome P-450 CYP1B1 Endometriosis Endometrium Ovarian Diseases Peritoneal Diseases Adult Case-Control Studies Cross-Sectional Studies Cytochrome P-450 CYP1A1 Cytochrome P-450 CYP1A1 Cytochrome P-450 CYP1B1 Cytochrome P-450 CYP1B1 Endometriosis Endometriosis Endometrium Female Humans Ovarian Diseases Ovarian Diseases

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