Study of estrogen metabolism in peritoneal lesions of women with endometriosis

• Grant number: 10/02412-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2010
• End date: August 31, 2013
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Rui Alberto Ferriani
• Grantee: Carla de Azevedo Piccinato Camargo
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil

Abstract

An estimated 10% of women in reproductive age suffer from endometriosis, an estrogen-dependent disease. The bioavailability of the local estrogen which is important to the maintenance of the disease is determined by the balance between production and break down (metabolism). Furthermore, the progression of endometriosis is directly influenced by the expression and activity of the enzymes involved in the synthesis and metabolism of estrogens. Estrogen synthesis has been widely explored, particularly in the study of aromatase expression and activity in endometriotic lesions. In contrast, only few studies focus on the impact of estrogen metabolism in the pathogenesis of endometriosis. The aim of the present proposal is to investigate the involvement of enzymes responsible for oxidative (CYP1A2, 1B1 e 3A4) and conjugative (UDP-glucurosyltransferase and estrogen sulphotransferase) metabolism of estrogens in endometriosis, since most of those metabolizing enzymes hasn't been described yet in endometriotic lesions. The proposal has 3 phases, as follows. In the first one it is proposed to validate techniques on collection and storage of samples to ensure high quality of RNA for the molecular studies. The second stage comprehends gene expression studies by real time PCR and determination of enzyme concentration using Western Blotting. The last phase concerns the enzyme activity study by which estrogen metabolite concentration will be determinded in cell culture (and peritoneal fluid) using specific inhibitors of metabolizing enzymes. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PICCINATO, CARLA A.; NEME, ROSA M.; TORRES, NATALIA; SILVERIO, RENATA; PAZZINI, VANESSA BITENCOURT; ROSA E SILVA, JULIO C.; FERRIANI, RUI A.. Is cytochrome P450 3A4 regulated by menstrual cycle hormones in control endometrium and endometriosis?. Molecular and Cellular Biochemistry, v. 427, n. 1-2, p. 81-89, MAR 2017. (10/02412-6)

PICCINATO, CARLA A.; MALVEZZI, HELENA; GIBSON, DOUGLAS A.; SAUNDERS, PHILIPPA T. K.. Contribution of intracrine oestrogens to the aetiology of endometriosis. JOURNAL OF MOLECULAR ENDOCRINOLOGY, v. 61, n. 2, p. T253-T270, AUG 2018. (10/02412-6)

PICCINATO, CARLA A.; NEME, ROSA M.; TORRES, NATALIA; VICTOR, ELIVANE DA SILVA; BRUDNIEWSKI, HELOISA F.; ROSA E SILVA, JULIO C.; FERRIANI, RUI A.. Enhanced UGT1A1 Gene and Protein Expression in Endometriotic Lesions. REPRODUCTIVE SCIENCES, v. 25, n. 9, p. 1371-1375, SEP 2018. (10/02412-6)

PICCINATO, CARLA A.; NEME, ROSA M.; TORRES, NATALIA; SANCHES, LIVIA RENTA; MATTOS CRUZ DEROGIS, PRISCILLA BENTO; BRUDNIEWSKI, HELOISA F.; ROSA E SILVA, JULIO C.; FERRIANI, RUI A.. Effects of steroid hormone on estrogen sulfotransferase and on steroid sulfatase expression in endometriosis tissue and stromal cells. JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, v. 158, p. 117-126, APR 2016. (10/02412-6)