Suicide inactivation of aromatase in human placenta and uterine leiomyoma by 5α-dihydronorethindrone, a metabolite of norethindrone, and its effect on steroid-producing enzymes
| Autor: | Takaya Tamura, Takara Yamamoto, Jo Kitawaki, Yoshio Osawa, Hiroji Okada |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Adult
medicine.medical_specialty Neoplasms Hormone-Dependent Norethisterone medicine.drug_class Placenta Endocrinology Diabetes and Metabolism medicine.medical_treatment Metabolite Mixed Function Oxygenases chemistry.chemical_compound Endocrinology Pregnancy Internal medicine medicine Animals Humans Aromatase Aromatase inhibitor Uterine leiomyoma Dose-Response Relationship Drug Leiomyoma biology Progestogen Aromatase Inhibitors General Medicine medicine.anatomical_structure Receptors Estrogen chemistry Estrogen Uterine Neoplasms biology.protein Female Rabbits Norethindrone Receptors Progesterone medicine.drug |
| Zdroj: | European Journal of Endocrinology. 130:634-640 |
| ISSN: | 1479-683X 0804-4643 |
| DOI: | 10.1530/eje.0.1300634 |
| Popis: | Yamamoto T, Tamura T, Kitawaki J, Osawa Y, Okada H. Suicide inactivation of aromatase in human placenta and uterine leiomyoma by 5α-dihydronorethindrone, a metabolite of norethindrone, and its effect on steroid-producing enzymes. Eur J Endocrinol 1994;130:634–40. ISSN 0804–4643 Norethindrone (NET; 17α-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 5α-dihydronorethindrone (5α-DHNET), a metabolite of NET that is not aromatizable, and the inhibitory effects of 5α-DHNET on human placental and uterine leiomyoma microsomal aromatase and other steroid synthetases. 5α-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 17α-hydroxylase, 21-hydroxylase or 11β-hydroxylase activities. These results suggest that 5α-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 |
| Databáze: | OpenAIRE |
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