title: Increased expression of CYP1A1 and CYP1B1 in ovarian/peritoneal endometriotic lesions.
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.
authors.affiliation: Hospital Israelita Albert EinsteinSão Paulo, Brazil Department of Gynaecology and ObstetricsSchool of Medicine of Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil cpiccinato@uwalumni.com.
authors.forename: Carla A
authors.initials: CA
authors.lastname: Piccinato
authors.affiliation: Hospital Israelita Albert EinsteinSão Paulo, Brazil Centro de Endometriose São PauloAv. República do Líbano, São Paulo, Brazil.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Neme
authors.affiliation: Hospital Israelita Albert EinsteinSão Paulo, Brazil.
authors.forename: Natália
authors.initials: N
authors.lastname: Torres
authors.affiliation: Department of Clinical PathologyHospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: Lívia Renta
authors.initials: LR
authors.lastname: Sanches
authors.affiliation: Department of Clinical PathologyHospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: Priscilla Bento Mattos
authors.initials: PB
authors.lastname: Cruz Derogis
authors.affiliation: Hospital Israelita Albert EinsteinSão Paulo, Brazil Centro de Endometriose São PauloAv. República do Líbano, São Paulo, Brazil.
authors.forename: Heloísa F
authors.initials: HF
authors.lastname: Brudniewski
authors.affiliation: Department of Gynaecology and ObstetricsSchool of Medicine of Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Júlio C Rosa
authors.initials: JC
authors.lastname: E Silva
authors.affiliation: Department of Gynaecology and ObstetricsSchool of Medicine of Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Rui A
authors.initials: RA
authors.lastname: Ferriani
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics* / Q000378:metabolism; D004715:Endometriosis / Q000235:genetics* / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D006801:Humans; D010049:Ovarian Diseases / Q000235:genetics* / Q000378:metabolism; D010532:Peritoneal Diseases / Q000235:genetics* / Q000378:metabolism
chemical_list: C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1