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

• Published in: Fertility and sterility Vol. 86; no. 2; pp. 291 - 297
• Main Authors: Murakami, Koichi, Nomura, Kazuhito, Shinohara, Kazunori, Kasai, Tadayuki, Shozu, Makio, Inoue, Masaki
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.2006; Elsevier Science
• Subjects: aromatase; Aromatase - genetics; Aromatase - metabolism; Aromatase Inhibitors - administration & dosage; Aromatase Inhibitors - pharmacology; Biological and medical sciences; Blotting, Western; Cells, Cultured; competitor; danazol; Danazol - administration & dosage; Danazol - pharmacology; Endometriosis; Endometriosis - enzymology; Endometriosis - pathology; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Kinetics; Medical sciences; Non tumoral diseases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Stromal Cells - drug effects; Stromal Cells - enzymology; Endometriosis; aromatase; danazol; competitor; Competition; Androgen; Enzyme; Gonadotropin; Estrogen synthase; Biological activity; Danazol; Mechanism; Female genital diseases; Fertility; Uterine diseases; Inhibitor; Antagonist; Stromal cell; Sex steroid hormone
• ISSN: 0015-0282; 1556-5653
• DOI: 10.1016/j.fertnstert.2005.12.074

To evaluate the inhibitory effect of danazol on estrogen (E) production in endometriosis. Prospective randomized study. Academic research unit of the department of obstetrics and gynecology in a university hospital. Thirteen patients with endometriosis. Danazol was added to the culture of endometriosis-derived stromal cells or suspensions of microsomes prepared from chocolate cysts. The aromatase activities as well as mRNA and protein levels of aromatase in endometriosis-derived stromal cells or microsomes of endometriosis were examined. 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 × 10 −6 M of calculated Ki and 2.9 × 10 −5 M of Ki′) of endometriosis microsomes. 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.