Intact progesterone receptors are essential to counteract the proliferative effect of estradiol in a genetically engineered mouse model of endometriosis

Zongjuan Fang, Sijun Yang, John P. Lydon, Franco Demayo, Mitsutoshi Tamura, Bilgin Gurates, Serdar E. Bulun

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

To determine the role of P and its nuclear receptor PR in the growth of ectopic uterine tissue of mice with or without a disrupted PR gene. Animal study. Academic medical center. Female wild-type (WT) and transgenic knockout mice for P receptor (PRKO). Endometriosis was induced in the following groups of ovariectomized adult mice: [1] untreated WT, [2] estradiol (E 2)-treated WT, [3] P-treated WT, [4] E 2 + P-treated WT, [5] untreated PRKO, [6] E 2-treated PRKO, and [7] E 2 + P-treated PRKO (n = 5 in each group). The size of ectopic uterine tissue in WT and PRKO mice were compared between the groups subjected to treatments with P or E 2. Tissue proliferating cell nuclear antigen (PCNA) levels were compared among these groups. Treatment with P only significantly decreased the size of WT ectopic uterine tissue. The untreated PRKO ectopic uterine tissue was significantly larger than WT tissue. Estradiol increased the size of ectopic uterine tissues, and this E 2-dependent growth could be suppressed by P in WT tissues but not in PRKO tissues. Finally, the hormone-dependent changes in ectopic uterine tissue size were accompanied by comparable alterations in PCNA levels. Intact PR in ectopic uterine tissue is essential to abolish E 2-dependent or -independent proliferation. We also suggest that ectopic uterine tissue is associated with significantly increased resistance to P action and increased predisposition to E 2-dependent proliferation in the absence of PR. Overall, these findings support the hypothesis that P resistance in human endometriosis may be due to the absence of sufficient levels of functional PR in this tissue.

Original languageEnglish (US)
Pages (from-to)673-678
Number of pages6
JournalFertility and Sterility
Volume82
Issue number3
DOIs
StatePublished - Sep 2004

Keywords

  • Endometriosis
  • PRKO mice
  • endometrium
  • estradiol
  • knockout mice
  • progesterone
  • progesterone receptor
  • uterus

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

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