Effects of hormonally active agents on steroid hormone receptor expression and cell proliferation in the myometrium of ovariectomized macaques

Toxicol Pathol. 2011 Apr;39(3):508-15. doi: 10.1177/0192623311401045. Epub 2011 Mar 16.

Abstract

Hormone replacement therapy and selective estrogen receptor modulators have been controversial treatment options for postmenopausal women because of their potential health benefits and/or risks. In this study, we determine the effects of the hormonally active compounds, conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), CEE + MPA, and tamoxifen (TAM) on the myometrium of ovariectomized macaques. Immunoexpression of estrogen receptor-α (ERα), progesterone receptor (PR), and Ki-67 in the myometrium is assessed. We found no significant difference in ERα myometrial expression in the CEE, MPA, and CEE + MPA treatment groups, but there was a significant decrease in expression in animals administered TAM versus controls. Conjugated equine estrogen-, TAM-, and CEE + MPA-treated animals had significantly increased expression of PR in myometrial cells and there was no difference in PR expression in cells from MPA-treated animals versus control animals. Myometrial cell proliferation did not significantly differ between the controls and any of the treatment groups, although normalized Ki-67 values were somewhat higher in the CEE and TAM groups. These data suggest that ERα and PR expression in the myometrium is influenced by treatment with hormonally active agents.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Proliferation
  • Estrogen Receptor alpha / metabolism
  • Estrogens, Conjugated (USP) / pharmacology*
  • Female
  • Hormone Replacement Therapy / methods
  • Ki-67 Antigen / metabolism
  • Macaca fascicularis
  • Medroxyprogesterone Acetate / pharmacology*
  • Myometrium / drug effects*
  • Myometrium / metabolism
  • Ovariectomy
  • Receptors, Progesterone / drug effects*
  • Selective Estrogen Receptor Modulators / pharmacology
  • Tamoxifen / pharmacology*

Substances

  • Estrogen Receptor alpha
  • Estrogens, Conjugated (USP)
  • Ki-67 Antigen
  • Receptors, Progesterone
  • Selective Estrogen Receptor Modulators
  • Tamoxifen
  • Medroxyprogesterone Acetate