Danazol inhibits aromatase activity of endometriosis-derived stromal cells by a competitive mechanism

Fertil Steril. 2006 Aug;86(2):291-7. doi: 10.1016/j.fertnstert.2005.12.074. Epub 2006 Jun 27.

Abstract

Objective: To evaluate the inhibitory effect of danazol on estrogen (E) production in endometriosis.

Design: Prospective randomized study.

Setting: Academic research unit of the department of obstetrics and gynecology in a university hospital.

Patient(s): Thirteen patients with endometriosis.

Intervention(s): Danazol was added to the culture of endometriosis-derived stromal cells or suspensions of microsomes prepared from chocolate cysts.

Main outcome measure(s): The aromatase activities as well as mRNA and protein levels of aromatase in endometriosis-derived stromal cells or microsomes of endometriosis were examined.

Result(s): Danazol treatment with a concentration greater than 10(-6) M significantly suppressed aromatase activity of endometriosis-derived stromal cells under basal and prostaglandin E(2) (PGE(2))-stimulated conditions. Danazol (10(-5) M) did not affect mRNA and protein levels of aromatase. Danazol competitively inhibited aromatase activity (by 1.7 x 10(-6) M of calculated Ki and 2.9 x 10(-5) M of Ki') of endometriosis microsomes.

Conclusion(s): Danazol competitively inhibited aromatase activity in endometriosis-derived stromal cells without affecting either the mRNA or protein levels of aromatase. These results indicate the efficacy of local application of danazol to endometriotic lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aromatase / genetics
  • Aromatase / metabolism*
  • Aromatase Inhibitors / administration & dosage*
  • Aromatase Inhibitors / pharmacology
  • Blotting, Western
  • Cells, Cultured
  • Danazol / administration & dosage*
  • Danazol / pharmacology
  • Endometriosis / enzymology*
  • Endometriosis / pathology
  • Female
  • Humans
  • Kinetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stromal Cells / drug effects
  • Stromal Cells / enzymology*

Substances

  • Aromatase Inhibitors
  • RNA, Messenger
  • Aromatase
  • Danazol