Effect of letrozole on estradiol production and P450 aromatase messenger RNA expression of cultured luteinized granulosa cells from women with and without endometriosis

Fertil Steril. 2012 Jul;98(1):131-5. doi: 10.1016/j.fertnstert.2012.03.055. Epub 2012 May 10.

Abstract

Objective: To compare the estradiol production and P450 aromatase messenger RNA (mRNA) expression of cultured luteinized granulosa cells and the effect of letrozole on these parameters between women with and without endometriosis.

Design: In vitro assays.

Setting: Reproductive medical center.

Patient(s): Patients undergoing in vitro fertilization (IVF): 23 patients with endometriosis and 19 controls without endometriosis.

Intervention(s): Luteinized granulosa cells examined for estradiol levels and P450 aromatase mRNA expression in conditioned media at different letrozole concentrations of 0.0, 0.1, 1.0, and 10.0 μmol/L.

Main outcome measure(s): Estradiol levels of the conditioned medium measured with an enzyme-linked immunosorbent assay (ELISA) kit and P450 aromatase mRNA expression determined by quantitative reverse transcription-polymerase chain reaction (QT RT-PCR).

Result(s): The estradiol concentration of the conditioned media and P450 aromatase mRNA expression in the endometriosis group were statistically significantly lower than that of the control group, irrespective of letrozole concentrations. A statistically significant reduction of these two parameters was observed in both endometriosis and control groups at letrozole concentrations of 1 μmol/L and 10 μmol/L, but there were no statistically significant differences between letrozole concentrations of 1 μmol/L and 10 μmol/L. The number of high-quality embryos in the endometriosis group was statistically significantly lower than that of the control group.

Conclusion(s): Lower estradiol production and P450 aromatase mRNA expression of cultured granulosa cells were found in women with endometriosis. Letrozole in the conditioned media further reduced these parameters.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aromatase / genetics*
  • Aromatase / metabolism
  • Aromatase Inhibitors / pharmacology
  • Case-Control Studies
  • Cells, Cultured
  • Endometriosis / genetics
  • Endometriosis / metabolism
  • Endometriosis / pathology*
  • Estradiol / biosynthesis*
  • Estradiol / metabolism
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Granulosa Cells / cytology
  • Granulosa Cells / drug effects*
  • Granulosa Cells / metabolism
  • Granulosa Cells / pathology
  • Humans
  • Letrozole
  • Luteinization / drug effects
  • Luteinization / genetics
  • Luteinization / metabolism
  • Nitriles / pharmacology*
  • Ovarian Diseases / genetics
  • Ovarian Diseases / metabolism
  • Ovarian Diseases / pathology*
  • Primary Cell Culture
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Triazoles / pharmacology*

Substances

  • Aromatase Inhibitors
  • Nitriles
  • RNA, Messenger
  • Triazoles
  • Estradiol
  • Letrozole
  • Aromatase