Donata Ponikwicka-Tyszko1, Marcin Chrusciel1, Joanna Stelmaszewska1, Piotr Bernaczyk1, Maria Sztachelska1, Iwona Sidorkiewicz1, Milena Doroszko1, Jakub Tomaszewski1, Juha S Tapanainen1, Ilpo Huhtaniemi1, Slawomir Wolczynski1, Nafis A Rahman1. 1. Department of Biology and Pathology of Human Reproduction (D.P.-T., M.S., S.W.), Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, Poland; Department of Physiology (M.C., M.D., I.H., N.A.R.), Institute of Biomedicine, University of Turku, 20520 Turku, Finland; Department of Hormonal Action Mechanisms (M.C.), Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10748 Olsztyn, Poland; Department of Reproduction and Gynecological Endocrinology (J.S., I.S., S.W., N.A.R.), Medical University of Bialystok, 15-276 Bialystok, Poland; Department of Pathomorphology (P.B.), Medical University of Bialystok, 15269 Bialystok, Poland; Tomaszewski Medical Center of Obstetrics and Gynecology (J.To.), 15-224 Bialystok, Poland; Department of Obstetrics and Gynecology (J.Ta.), University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland; and Institute of Reproductive and Developmental Biology (I.H.), Imperial College London, W12 0NN London, United Kingdom.
Abstract
CONTEXT: FSH receptor (FSHR), besides being expressed in gonads, is also expressed in some extragonadal tissues at low levels. OBJECTIVE: We examined the functional expression of FSHR in different types of endometriotic lesions. DESIGN: Extensive studies were carried out to detect functional FSHR expression and FSH-stimulated estrogen production in ovarian endometriomas and recto-vaginal endometriotic nodules (RVEN). Normal endometrium, ovary, and myometrium tissues from nonpregnant cycling women served as controls. SETTINGS: This laboratory-based study was carried out on tissue specimens from patients with endometriosis and healthy donors. RESULTS: Endometriotic lesions and normal secretory-phase endometrium showed FSHR expression at both mRNA and protein level. RVEN and ovarian endometrioma demonstrated up-regulated CYP19A1, dependent on the activation of CYP19A1 proximal promoter II. Estrogen receptor-β (ESR2) expression was significantly increased in RVEN vs normal endometrium. Recombinant human FSH stimulation of RVEN explants significantly increased estradiol production and CYP19A1 and ESR2 expression. FSHR was up-regulated in recombinant human FSH-stimulated endometrial and decidualized stromal cells with increased CYP19A1 expression. CONCLUSIONS: We described a novel functional FSHR expression, where FSH-stimulated CYP19A1 expression and estrogen production in RVEN are demonstrated. This locally FSH-induced estrogen production may contribute to the pathology, development, progression, and severity of RVEN.
CONTEXT: FSH receptor (FSHR), besides being expressed in gonads, is also expressed in some extragonadal tissues at low levels. OBJECTIVE: We examined the functional expression of FSHR in different types of endometriotic lesions. DESIGN: Extensive studies were carried out to detect functional FSHR expression and FSH-stimulated estrogen production in ovarian endometriomas and recto-vaginal endometriotic nodules (RVEN). Normal endometrium, ovary, and myometrium tissues from nonpregnant cycling women served as controls. SETTINGS: This laboratory-based study was carried out on tissue specimens from patients with endometriosis and healthy donors. RESULTS:Endometriotic lesions and normal secretory-phase endometrium showed FSHR expression at both mRNA and protein level. RVEN and ovarian endometrioma demonstrated up-regulated CYP19A1, dependent on the activation of CYP19A1 proximal promoter II. Estrogen receptor-β (ESR2) expression was significantly increased in RVEN vs normal endometrium. Recombinant human FSH stimulation of RVEN explants significantly increased estradiol production and CYP19A1 and ESR2 expression. FSHR was up-regulated in recombinant human FSH-stimulated endometrial and decidualized stromal cells with increased CYP19A1 expression. CONCLUSIONS: We described a novel functional FSHR expression, where FSH-stimulated CYP19A1 expression and estrogen production in RVEN are demonstrated. This locally FSH-induced estrogen production may contribute to the pathology, development, progression, and severity of RVEN.
Authors: Huizhen Wang; Jacob May; Viktor Butnev; Bin Shuai; Jeffrey V May; George R Bousfield; T Rajendra Kumar Journal: Mol Cell Endocrinol Date: 2016-08-22 Impact factor: 4.102