Eur J Endocrinol
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DOI: 10.1530/eje.0.1300634
European Journal of Endocrinology, Vol 130, Issue 6, 634-640
Copyright © 1994 by European Society of Endocrinology
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Suicide inactivation of aromatase in human placenta and uterine leiomyoma by 5{alpha}-dihydronorethindrone, a metabolite of norethindrone, and its effect on steroid-producing enzymes

Takara Yamamoto, Takaya Tamura, Jo Kitawaki, Yoshio Osawa and Hiroji Okada

Yamamoto T, Tamura T, Kitawaki J, Osawa Y, Okada H. Suicide inactivation of aromatase in human placenta and uterine leiomyoma by 5{alpha}-dihydronorethindrone, a metabolite of norethindrone, and its effect on steroid-producing enzymes. Eur J Endocrinol 1994;130:634–40. ISSN 0804–4643

Norethindrone (NET; 17{alpha}-ethynyl-19-nortestosterone), a progestogen component of the contraceptive pill, irreversibly inhibits aromatase activity in human placental microsomes. However, it is known also to be aromatized in vitro and in vivo to produce a biologically very active estrogen called ethynylestradiol (EE2). It is therefore inappropriate to administer a high dose of NET to estrogendependent cancer patients for a prolonged time period. In this study, we focused on 5{alpha}-dihydronorethindrone (5{alpha}-DHNET), a metabolite of NET that is not aromatizable, and the inhibitory effects of 5{alpha}-DHNET on human placental and uterine leiomyoma microsomal aromatase and other steroid synthetases. 5{alpha}-Dihydronorethindrone showed weak affinity for both estrogen and progestogen receptors. It inhibited significantly human placental aromatase activity in a dose-dependent manner (Ki = 9.0 µmol/l; Kinact = 0.024/min), as well as that of uterine leiomyoma, but did not influence cholesterol side-chain cleavage or 17{alpha}-hydroxylase, 21-hydroxylase or 11β-hydroxylase activities. These results suggest that 5{alpha}-DHNET may be useful as an aromatase inhibitor, whose use in large doses is expected to reduce the size of estrogen-dependent tumors.

Takara Yamamoto, Department of Obstetrics and Gynecology, Kawaramachi-Hirokoji, Kamikyo-Ku, Kyoto 602, Japan






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Copyright © 1994 European Society of Endocrinology.