Synthesis of catechol estrogens by human uterus and leiomyoma.
Homogenates of human endometrial, myometrial and leiomyoma tissues were incubated with (2,4,6,7-3H)-estradiol and tritiated catechol estrogens were isolated and identified. Though 2- and 4-hydroxylations were about the same in endometrium, 4-hydroxylation was two to four fold higher than 2-hydroxylation in myometrium and leiomyoma. However, endometrium showed greater capacity to form both 2- and 4-hydroxyestrogens than the other two tissues. Both 2- and 4-hydroxylations were significantly less than in myometrium. In view of the reports indicating that inhibitors of catechol 0-methyl transferase (COMT) might act as antineoplastic agents due to their interference with t-RNA methylases and since catechol estrogens inhibit COMT, the present results suggest that endogenous synthesis of catechol estrogens may play an important role in the pathophysiology of uterine leiomyoma.
D001189:Aryl Hydrocarbon Hydroxylases; D002250:Carbon Radioisotopes; D002396:Catechols / Q000096:biosynthesis*; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D004717:Endometrium / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000096:biosynthesis*; D002393:Estrogens, Catechol; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism*; D009215:Myometrium / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism; D014316:Tritium; D014594:Uterine Neoplasms / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism*
D002250:Carbon Radioisotopes; D002396:Catechols; D004967:Estrogens; D002393:Estrogens, Catechol; D014316:Tritium; D004958:Estradiol; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; C020120:estrogen 2-hydroxylase