Functional Expression of FSH Receptor in Endometriotic Lesions

J Clin Endocrinol Metab. 2016 Jul;101(7):2905-14. doi: 10.1210/jc.2016-1014. Epub 2016 May 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aromatase / genetics*
  • Aromatase / metabolism
  • Case-Control Studies
  • Endometriosis / genetics*
  • Endometriosis / pathology
  • Endometrium / drug effects
  • Endometrium / metabolism*
  • Endometrium / pathology
  • Estradiol / metabolism
  • Estrogen Receptor beta / physiology
  • Female
  • Follicle Stimulating Hormone / pharmacology
  • Gene Expression Regulation / drug effects
  • Humans
  • Ovarian Diseases / genetics
  • Ovarian Diseases / pathology
  • Promoter Regions, Genetic / drug effects
  • Receptors, FSH / genetics*
  • Receptors, FSH / metabolism
  • Rectal Diseases / genetics*
  • Rectal Diseases / pathology
  • Vaginal Diseases / genetics*
  • Vaginal Diseases / pathology
  • Young Adult

Substances

  • Estrogen Receptor beta
  • Receptors, FSH
  • Estradiol
  • Follicle Stimulating Hormone
  • Aromatase
  • CYP19A1 protein, human