Effects of Tibolone on Sulfatase Pathway of Estrogens Metabolism and on Growth of MCF-7 Human Breast Tumors Implanted in Ovariectomized Nude Mice
| Autor: | Agnès Noël, Helenius Kloosterboer, Jean-Michel Foidart, Francis Frankenne, Monique Putman, Madeleine Lemaire, Joëlle Desreux |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Norpregnenes medicine.drug_class Ovariectomy medicine.medical_treatment Mice Nude Tibolone Biology Mice Estrogen Receptor Modulators Cell Line Tumor Internal medicine medicine Animals Humans Cell Proliferation Sulfatase Mammary Neoplasms Experimental Obstetrics and Gynecology Estrogens Hormone replacement therapy (menopause) Xenograft Model Antitumor Assays Transplantation Endocrinology Reproductive Medicine MCF-7 Estrogen Ovariectomized rat Female Sulfatases Progestin hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Gynecologic and Obstetric Investigation. 63:31-38 |
| ISSN: | 1423-002X 0378-7346 |
| Popis: | Background: The benefits of estrogen plus progestin in healthy post-menopausal women remain uncertain. Tibolone, with its in vitro documented inhibitory effects on estrogens metabolism and its selective action on breast, may be an alternative that could favorably influence the health benefit of hormone replacement therapy. Methods: We studied the effect of tibolone on the tumor growth of MCF-7 cells implanted in 40 ovariectomized nude mice, receiving subcutaneous pellets of 17β-estradiol, estrone, estrone-sulfate or vehicle, and daily gavages of tibolone or placebo. Results: Tibolone, although used at high dose, did not stimulate nor inhibit the estrogen-induced tumors, nor the tumors in estrogen-deprived mice. Measurements of plasma levels of estrogens indicated that tibolone potently stimulated sulfotransferase activity, but intra-tumor levels of estrogens were not significantly modified by tibolone. Conclusions: This in vivo study performed with high dose of orally administered tibolone that allowed its hepatic conversion into active metabolites has shown no significant effect on breast tumors growth. Tibolone increased the circulating sulfated estrogens by its activity on the hepatic sulfation but not the intra-tumor levels of estrogens (free or sulfated). However, further studies of dose-response curve and molecular markers are needed to exclude definitely a stimulatory effect of tibolone on tumor growth. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|