Gonadotropin-positive pituitary tumors accompanied by ovarian tumors in aging female ERβ-/- mice

Xiaotang Fan, Chiara Gabbi, Hyun Jin Kim, Guojun Cheng, Leif C. Andersson, Margaret Warner, Jan Åke Gustafsson

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

At 2 years of age, 100% (23/23) of ERβ-/- female mice have developed large pituitary and ovarian tumors. The pituitary tumors are gonadotropin-positive and the ovarian tumors are sex cord (less differentiated) and granulosa cell tumors (differentiated and estrogen secreting). No male mice had pituitary tumors and no pituitary or ovarian tumors developed in ERβ-/- mice or in ERβ-/- double knockout mice. The tumors have high proliferation indices, are ERα-positive, ERβ-negative, and express high levels of nuclear phospho-SMAD3. Mice with granulosa cell tumors also had hyperproliferative endometria. The cause of the pituitary tumors appeared to be excessive secretion of gonadotropin releasing hormone (GnRH) from the hypothalamus resulting from high expression of NPY. The ovarian phenotype is similar to that seen in mice where inhibin is ablated. The data indicate that ERβ plays an important role in regulating GnRH secretion. We suggest that in the absence of ERβ, the proliferative action of FSH/SMAD3 is unopposed and the high proliferation leads to the development of ovarian tumors. The absence of tumors in the ERβ-/- mice suggests that tumor development requires the presence of ERα.

Original languageEnglish (US)
Pages (from-to)6453-6458
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number14
DOIs
StatePublished - Apr 6 2010

Keywords

  • Estrogen receptor β (ERβ)
  • Follicle stimulating hormone (FSH)
  • Gonadotropin releasing hormone (GnRH)
  • Pituitary
  • TGFβ

ASJC Scopus subject areas

  • General

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