Species-specific pharmacology of antiestrogens: role of metabolism
The nonsteroidal antiestrogen tamoxifen exhibits a paradoxial space species pharmacology. The drug is a full estrogen in the mouse, a partial estrogen/antiestrogen in humans and the rat, and an antiestrogen in the chick oviduct. Inasmuch as tamoxifen has antiestrogenic effects in vitro, differential metabolism of tamoxifen to estrogens might occur in the species in which it has antiestrogen pharmacology. Tamoxifen or its metabolite 4-hydroxytamoxifen could lose the alkylaminoethane side chain to form the estrogenic compound metabolite E of bisphenol. Sensitive metabolic studies with (/sup 3/H)tamoxifen in chicks, rats, and mice identified 4-hydroxytamoxifen as the major metabolite. Athymic mice with transplanted human breast tumors can be used to study the ability of tamoxifen to stimulate tissue or tumor growth. Estradiol caused the growth of transplanted breast cancer cells into solid tumors and a uterotrophic response. However, tamoxifen does not support tumor growth when administered alone, although it stimulates uterines growth. Since a similar profile of metabolites is sequestered in human mouse tissues, these studies strongly support the concept that the drug can selectively stimulate or inhibit events in the target tissues of different species without hometabolic intervention.
- Research Organization:
- Univ. of Wisconsin Clinical Cancer Center, Madison (USA)
- OSTI ID:
- 6924617
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 46:5
- Country of Publication:
- United States
- Language:
- English
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ESTROGENS
BIOCHEMICAL REACTION KINETICS
METABOLISM
EXPERIMENTAL NEOPLASMS
TRANSPLANTS
MAMMARY GLANDS
NEOPLASMS
CHICKENS
METABOLITES
MICE
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMALS
BIRDS
BODY
DISEASES
FOWL
GLANDS
HORMONES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
ORGANS
REACTION KINETICS
RODENTS
STEROID HORMONES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques