Use of letrozole as a chemopreventive agent in aromatase overexpressing transgenic mice

Roopa Luthra, Nameer Kirma, Jeremy Jones, Rajeshwar Rao Tekmal

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Our recent studies have shown that overexpression of aromatase results in increased tissue estrogenic activity and induction of hyperplastic and dysplastic lesions in mammary glands, and gynecomastia and testicular cancer in male aromatase transgenic mice. Our studies also have shown that aromatase overexpression-induced changes in mammary glands can be abrogated with very low concentrations of letrozole, an aromatase inhibitor without any effect on normal physiology. In the present study, we have examined the effect of prior low dose letrozole treatment on pregnancy and lactation. We have also investigated the effect of low dose letrozole treatment on subsequent mammary growth and biochemical changes in these animals. There was no change in the litter size, birth weight and no visible birth defects in letrozole-treated animals. Although, there was an insignificant increase in mammary growth in aged animals after 6 weeks of letrozole treatment, the levels of expression of estrogen receptor, progesterone receptor and genes involved in cell cycle and cell proliferation remained low compared to control untreated animals. These observations indicate that aromatase inhibitors such as letrozole can be used as chemopreventive agents without effecting normal physiology in aromatase transgenic mice.

Original languageEnglish (US)
Pages (from-to)461-467
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume86
Issue number3-5
DOIs
StatePublished - Sep 2003
Externally publishedYes

Keywords

  • Aromatase
  • Aromatase inhibitors
  • Chemoprevention
  • Tamoxifen
  • Transgenic mice

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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