Transdominant suppression of estrogen receptor signaling by progesterone receptor ligands in uterine leiomyoma cells.

Abstract

Uterine leiomyomas develop in reproductive-age women with high frequency and are dependent on the production of ovarian hormones. While it is generally accepted that these tumors are estrogen (E(2))-responsive, the role of progesterone (P(4)) in modulating tumor growth is less clear. In the present study, an in vivo/in vitro rat model was used to characterize progesterone receptor (PR) isoform expression in uterine leiomyoma and investigate PR signaling using progestins and antiprogestins in the leiomyoma-derived cell line ELT-3. PR-A was the predominant isoform expressed in normal myometrium, leiomyomas and ELT3 cells. In the normal myometrium, PR-A and PR-B levels varied during the estrous cycle with low ratios of PR-A relative to PR-B (PR-A/PR-B) coinciding with times of cell proliferation. Although PR ligands had no effect on basal levels of uterine leiomyoma cell proliferation in vitro, both progestins and antiprogestins inhibited E(2)-stimulated cell proliferation. In addition, E(2)-stimulated transactivation of an estrogen-response-element reporter gene as well as E(2)-induced upregulation of the PR were also inhibited by PR ligands. These data indicate that PR ligands can transdominantly suppress estrogen receptor signaling and stimulation of uterine leiomyoma cell growth.

• Authors: Leslie C Hodges, Kevin D Houston, Deborah S Hunter, Robin Fuchs-Young, Zhiming Zhang, Richard C Wineker, Cheryl L Walker
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 196 Issue 1-2 Pg. 11-20 (Oct 31 2002) ISSN: 0303-7207 [Print] Ireland
• PMID: 12385821 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Ligands
• Progestins
• Receptors, Estrogen
• Receptors, Progesterone
• progesterone receptor A
• progesterone receptor B
• Estradiol

Topics

• Animals
• Cell Division (drug effects)
• Estradiol (pharmacology)
• Estrous Cycle (metabolism)
• Female
• Leiomyoma (pathology)
• Ligands
• Myometrium (cytology)
• Progestins (pharmacology)
• Rats
• Receptors, Estrogen (physiology)
• Receptors, Progesterone (analysis, physiology)
• Signal Transduction (drug effects)
• Transcription, Genetic (drug effects)
• Tumor Cells, Cultured
• Uterine Neoplasms (pathology)