Aromatase and other steroidogenic genes in endometriosis: Translational aspects

E. Attar, S. E. Bulun*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

176 Scopus citations

Abstract

Endometriosis is a common, chronic and estrogen-dependent gynaecological disorder associated with pelvic pain and infertility. In addition to, or perhaps as a consequence of, immune, environmental and genetic factors, endometriotic lesions show high estradiol (E2) biosynthesis and low E2 inactivation compared with normal endometrium. Current medical therapies of pain, which aim to lower circulating E2 concentrations, are not effective in at least half of these patients. We and others recently demonstrated the expression of a few steroidogenic genes in endometriosis. The most important genes in this group are steroidogenic acute regulatory protein (StAR) and aromatase. Both are essential for E2 production. Prostaglandin E2 (PGE2) is the most potent known stimulator of both StAR and aromatase. PGE2 production in endometriosis is up-regulated by increased levels of the enzyme cyclo-oxygenase-2 (COX-2) in this tissue. COX-2 in turn is stimulated by E2, interleukin-1β (IL-1β) and PGE2 itself in endometrial and endometriotic cells. Thus, there is a positive feedback loop that favours continuous formation of E2 and PGE2 in endometriosis. These basic findings led to recent phase-II studies employing aromatase inhibitors in the treatment of endometriosis. Aromatase inhibitors treat both postmenopausal and premenopausal endometriosis at least as effectively as the existing medical treatments. In premenopausal women, we and others administered aromatase inhibitors in combination with an ovarian-suppressant treatment. In this review, we emphasize the most recent basic studies in detail and provide a short summary of recent clinical trials.

Original languageEnglish (US)
Pages (from-to)49-56
Number of pages8
JournalHuman Reproduction Update
Volume12
Issue number1
DOIs
StatePublished - Jan 2006

Keywords

  • Aromatase
  • Aromatase inhibitors
  • Cyclo-oxygenase-2
  • Endometriosis
  • Steroidogenic acute regulatory protein

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

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