Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Raynaud JP (1973) Influence of rat estradiol binding plasma protein (EBP) on uterotrophic activity. Steroids 21: 249–258.
Robyn C, M Vekemans, M Rozencweig, D Chigot and JP Raynaud (1978) Double-blind crossover clinical pharmacology study comparing Moxestrol (R-2858) and ethinyl estradiol in postmenopausal women. J Clin Pharmcol 18: 29–34.
Bouton MM and JP Raynaud (1979) The relevance of interaction kinetics in determining biological response to estrogens. Endocrinology 105: 509–515.
Salmon J, D Coussediere, C Cousty and JP Raynaud (1983) Pharmacokinetics and metabolism of Moxestrol in animals, rat, dog and monkey. J. Steroid Biochem 19: 1223–1234.
Li JJ and SA Li (1990) Estrogen carcinogenesis in hamster tissues: A critical review. Endocrine Rev 11: 524–531.
Li JJ, SA Li, TD Oberley, M Metzler and JA Parsons (1993) Further comparisons of carcinogenic activities of various natural and synthetic estrogens in the hamster kidney: Relation to proximal tubular cell proliferation in-vitro. Cancer Res, In press.
Li JJ and SA Li (1987) Estrogen carcinogenesis in Syrian hamster tissues: role of metabolism. Federation Proc 46: 1858–1863.
Gotteschlich R and M Metzler (1980) Metabolic fate of diethylstilbestrol in Syrian golden hamster, a susceptible species for diethylstilbestrol carcinogenicity. Xenobiotica 10: 317–327.
Liehr JG (1984) Modulation of estrogen-induced carcinogenesis by chemical modifications. Arch Toxicol 55: 119–122.
Tsibris JCM and PM McGuire (1977) Microsomal activation of estrogens and binding to nucleic acids and proteins. Biochem Biophys Res Commun 78: 411–417.
Salmon J, D Coussediere, C Cousty and JP Raynaud (1983) Pharmacokinetics and metabolism of moxestrol in humans. J Steroid Biochem 18: 565–573.
Oberley TD, Lauchner LJ, Pugh TD, Gonzalez A, Boldfarb S, Li SA, Li JJ (1989) Specific estrogen-induced cell proliferation of cultured Syrian hamster renal proximal tubular cells in serum-free chemically defined media. Proc Natl Acad Sci USA 86: 2107–2111.
Oberley TD, A Gonzalez, LJ Lauchner, LW Oberley and JJ Li (1991) Characterization of early kidney lesions in estrogen-induced tumors in the Syrian hamster. Cancer Res. 51; 1922–1929.
Purdy RH, JW Goldzieher, PW Le Quesne, S Abdel-Baky, CK Durocher, PH Moore and JS Rhim (1982) Active intermediates in carcinogenesis. In Merriam GR & Lipsett MB (eds): Catechol Estrogens, New York: Raven Press, Chapt 13.
Liehr JG, RH Purdy, JS Baran, EF Nutting, F Colton, E Randerath and K Randerath (1987) Correlation of aromatic hydroxylation of 11ß-substituted estrogens with morphological transformation in vitro but not with in vivo tumor induction by these hormones. Cancer Res 47: 2583–2588.
Li JJ, SA Li, JK Klicka, JA Parsons and LKT Lam (1983) Relative carcinogenic activity of various synthetic and natural estrogens in the hamster kidney. Cancer Res 43: 5200–5204.
Li JJ and S Nandi (1990) Hormones and carcinogenesis: laboratory studies. In: Becker KL (ed) Principles and practice of endocrinology and metabolism. J.B. Lippincott Co. Philadelphia, Chap. 225.
Li SA, JK Klicka and JJ Li (1985) Estrogen 2-/4-hydroxylase activity, catechol estrogen formation and implications for estrogen carcinogenesis. Cancer Res 45: 181–185.
Liehr JG (1990) Genotoxic effects of estrogens. Mutat Res 238: 269–276.
Haaf H, M Metzler and JJ Li (1992) Metabolism of [14C]-estrone in hamster and rat hepatic and renal microsomes: Species-, sex-and age-specific differences. J Steroid Biochem. In Press.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1992 Springer-Verlag New York, Inc.
About this paper
Cite this paper
Li, S.A., Li, J.J. (1992). Metabolism of Moxestrol in the Hamster Kidney: Significance for Estrogen Carcinogenesis. In: Li, J.J., Nandi, S., Li, S.A. (eds) Hormonal Carcinogenesis. Springer, New York, NY. https://doi.org/10.1007/978-1-4613-9208-8_15
Download citation
DOI: https://doi.org/10.1007/978-1-4613-9208-8_15
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4613-9210-1
Online ISBN: 978-1-4613-9208-8
eBook Packages: Springer Book Archive