Metabolism of Moxestrol in the Hamster Kidney: Significance for Estrogen Carcinogenesis
Moxestrol [11β-methoxy-17-ethinyl-1, 3, 5 (10)-estratriene-3,17β-diol or R 2858] is a potent estrogen in both animals and humans (1,2) and is used in Europe as a postmenopausal agent. Its estrogenic potency, depending on the biologic or biochemical parameters used, is approximately 10 to 100 times higher than 17β-estradiol (E2) (1) and about 5 times more potent than ethynylestradiol (EE2) (2). Its hormonal effectiveness has been attributed to the stability of the complex it forms with the estrogen receptor (3), its lower affinity for serum plasma proteins (1), and also the degree to which it is metabolized (4). In the hamster estrogeninduced-renal adenocarcinoma model, Moxestrol and EE2 exhibited similar estrogenic activities. Moxestrol, however, displayed potent tumorigenic activity at this organ site, eliciting 100% tumor incidence (5,6). In contrast, its parent compound EE2 exhibits only modest 10% renal tumor incidence when similarly administered. Since metabolism has been postulated by us (7) and others (8–10) to play a significant if not crucial role in neoplastic transformation of the hamster kidney, it becomes evidently pertinent to investigate the metabolism of Moxestrol in the kidney and liver of this species.
KeywordsLymphoma Estrogen Baran Prostaglandin NADPH
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