Citation

Yamamoto T, Tamura T, Kitawaki J, Osawa Y, Okada H. Eur. J. Endocrinol. 1994; 130(6): 634-640.

Copyright

(Copyright © 1994, BioScientifica)

DOI

10.1530/eje.0.1300634

PMID

8205267

Abstract

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 estrogen-dependent 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 mumol/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 11 beta-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.

Language: en

Keywords

Adult; Animals; Aromatase Inhibitors; Dose-Response Relationship, Drug; Female; Humans; Leiomyoma; Mixed Function Oxygenases; Neoplasms, Hormone-Dependent; Norethindrone; Placenta; Pregnancy; Rabbits; Receptors, Estrogen; Receptors, Progesterone; Uterine Neoplasms