A1 Refereed original research article in a scientific journal
Functional Expression of FSH Receptor in Endometriotic Lesions
Authors: Ponikwicka-Tyszko D, Chrusciel M, Stelmaszewska J, Bernaczyk P, Sztachelska M, Sidorkiewicz I, Doroszko M, Tomaszewski J, Tapanainen JS, Huhtaniemi I, Wolczynski S, Rahman NA
Publisher: ENDOCRINE SOC
Publication year: 2016
Journal:: Journal of Clinical Endocrinology and Metabolism
Journal name in source: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Journal acronym: J CLIN ENDOCR METAB
Volume: 101
Issue: 7
First page : 2905
Last page: 2914
Number of pages: 10
ISSN: 0021-972X
eISSN: 1945-7197
DOI: https://doi.org/10.1210/jc.2016-1014
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 studieswerecarried 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-beta (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 studieswerecarried 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-beta (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.
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