title: Effects of steroid hormone on estrogen sulfotransferase and on steroid sulfatase expression in endometriosis tissue and stromal cells.
abstract: Endometriosis is an estrogen-dependent disease that afflicts about 10% of women in their reproductive age, causing severe pain and infertility. The potential roles of female steroid hormones in modulating key estrogen-metabolizing enzymes, steroid sulfatase (STS) and estrogen sulfotransferase (SULT1E1), were investigated. The expression of STS and SULT1E1 mRNA in biopsy samples (n=78) of superficial and deep endometriotic lesions, eutopic endometrium of women with endometriosis and endometrium from control patients were compared according to the menstrual cycle phase. Increased STS gene expression was detected in superficial and deep-infiltrating lesions and a reduced SULT1E1 expression was also observed in the eutopic endometrium relative to the superficial lesions. Additionally, a significantly positive correlation was detected between STS and SULT1E1 mRNA expression levels in biopsy specimens collected from the endometriosis patients, and not in control individuals. The actions of female steroid hormones on SULT1E1 and STS expression were evidenced in endometriosis, revealed by increased expression levels in the luteal phase of the cycle. There was an increased STS expression in primary eutopic and ectopic endometrial stromal cells treated with estradiol and progesterone (representative of the luteal phase, n=3). Although an increased STS mRNA expression was observed in hormone-induced endometrial stromal cells in vitro, no difference could be detected between the hormone treatment groups in estradiol formation from estradiol sulfate measured by LC-MS-MS. Interestingly, a greater expression of STS was observed in stromal cells from eutopic endometrium with an agreement in estradiol formation originated from estradiol sulfate. The differential regulation of STS and SULT1E1 could provide insights for novel studies of the therapeutic use of STS inhibitors.
authors.affiliation: Hospital Israelita Albert Einstein, São Paulo, SP 05652-900, Brazil; Department of Gynaecology and Obstetrics, School of Medicine of Ribeirão Preto, Universidade de São Paulo, Brazil. Electronic address: cpiccinato@uwalumni.com.
authors.forename: Carla A
authors.initials: CA
authors.lastname: Piccinato
authors.affiliation: Hospital Israelita Albert Einstein, São Paulo, SP 05652-900, Brazil; Centro de Endometriose São Paulo, Av. República do Líbano, 460 São Paulo, SP 04502-000, Brazil. Electronic address: rosaneme@uol.com.br.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Neme
authors.affiliation: Hospital Israelita Albert Einstein, São Paulo, SP 05652-900, Brazil. Electronic address: natalia.torres@einstein.br.
authors.forename: Natália
authors.initials: N
authors.lastname: Torres
authors.affiliation: Department of Clinical Pathology, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. Electronic address: livia.sanches@einstein.br.
authors.forename: Lívia Renta
authors.initials: LR
authors.lastname: Sanches
authors.affiliation: Department of Clinical Pathology, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. Electronic address: priscilla.derogis@einstein.br.
authors.forename: Priscilla Bento Mattos Cruz
authors.initials: PBMC
authors.lastname: Derogis
authors.affiliation: Hospital Israelita Albert Einstein, São Paulo, SP 05652-900, Brazil; Centro de Endometriose São Paulo, Av. República do Líbano, 460 São Paulo, SP 04502-000, Brazil. Electronic address: helobrud@gmail.com.
authors.forename: Heloísa F
authors.initials: HF
authors.lastname: Brudniewski
authors.affiliation: Department of Gynaecology and Obstetrics, School of Medicine of Ribeirão Preto, Universidade de São Paulo, Brazil. Electronic address: juliocrs@usp.br.
authors.forename: Júlio C
authors.initials: JC
authors.lastname: Rosa E Silva
authors.affiliation: Department of Gynaecology and Obstetrics, School of Medicine of Ribeirão Preto, Universidade de São Paulo, Brazil. Electronic address: raferria@fmrp.usp.br.
authors.forename: Rui A
authors.initials: RA
authors.lastname: Ferriani
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D004715:Endometriosis / Q000097:blood / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D004967:Estrogens / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008597:Menstrual Cycle / Q000378:metabolism; D011374:Progesterone / Q000097:blood / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D043266:Steryl-Sulfatase / Q000235:genetics* / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism; D015238:Sulfotransferases / Q000235:genetics*
chemical_list: D004967:Estrogens; D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol; D015238:Sulfotransferases; C020122:estrone sulfotransferase; D043266:Steryl-Sulfatase
keywords: Endometrial stromal cells; Endometrium; Estradiol; Estrogen Metabolizing enzymes; Estrogen metabolism; Estrogen sulfates; Progesterone; STS; SULT1E1