Inhibitory effect of a new androstenedione derivative, 14 alpha-hydroxy-4-androstene-3,6,17-trione (14 alpha-OHAT) on aromatase activity of human uterine tumors.
The development of human uterine estrogen-dependent tumors is considered to be closely related to estrogen biosynthesis. This study examined whether or not 14 alpha-hydroxy-4-androstene-3,6,17-trione (14 alpha-OHAT), a new 4-androstene-3, 17-dione derivative synthesized microbiologically, inhibits estrogen biosynthetase (aromatase) activities of human uterine tumors (i.e. uterine endometrial cancer, uterine leiomyoma and uterine adenomyosis tissues). 14 alpha-OHAT inhibited aromatase activity in all uterine tumors, dose-dependently (0.1-10 microM). Moreover, 14 alpha-OHAT did not show the binding affinity to rabbit uterine cytosol-sex steroids, and it was not converted to estrogen in human placental preparations. Thus, 14 alpha-OHAT, an aromatase inhibitor, may be useful clinically as an endocrine chemotherapy for peri- or post-menopausal women with uterine estrogen-dependent tumors.
Yamamoto
T
T
Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Japan.
Fukuoka
M
M
Fujimoto
Y
Y
Kitawaki
J
J
Nakakoshi
M
M
Yoshihama
M
M
Okada
H
H
D000328:Adult; D000737:Androstenols / Q000494:pharmacology*; D000818:Animals; D001141:Aromatase / Q000032:analysis; D047072:Aromatase Inhibitors; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008875:Middle Aged; D010920:Placenta / Q000201:enzymology; D011817:Rabbits; D014594:Uterine Neoplasms / Q000201:enzymology*
D000737:Androstenols; D047072:Aromatase Inhibitors; C067637:14-hydroxyandrost-4-ene-3,6,17-trione; D001141:Aromatase