Abstract
Four newly synthesized estra-l,3,5(10)-triene-derivatives1,
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3-methoxy-17α-cyanomethyl-estra-l,3,5(10)-triene-17β-ol (I),
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3-methoxy-17α-rhodanomethyl-estra-l,3,5(10)-triene-17β-ol-tetrahydropyranylether (II),
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17/8-(N2032,N2032-dimethylhydrazinocarbonyloxy)-estra-l,3,5(10)-triene-3β-ol (III),
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3-methoxy-17-(N-phenylaminocarbonyloxy)-estra-l,3,5(10)-triene (IV),
were studied in subchronic toxicity tests in female rats. The drugs were given orally and compared to mestranol (V) which was used as a reference. Special histopathologic examination was performed in each rat with respect to pituitary morphology. Different pituitary responses to the applied estrogens were found with regard to hyperplasia of the adenohypophysis and interstitial haemosiderosis: 17β-hydroxy-17α-alkylsubstituted derivatives (I, II, V) were less effective than 17β-carbamyloxy-derivatives (III, IV). These findings may be related to differences in pituitary accumulation of the investigated compounds, indicating any disposition-effect-relationships.
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References
Fishman, J., Norton, B.: Relative Transport of Estrogens into the Central Nervous System. In: Pharmacology of Steroid Contraceptive Drugs. Garattini, S., Berendes, H. W. (eds.), pp. 37–42 New York: Raven Press 1977
Herlant, M., Pasteels, J. L.: Histophysiology of human anterior pituitary. Meth. Achiev. exp. Path. 3, 250–305 (1967)
Hobe, G., Schön, R., Schade, W.: Species differences in biotransformation of 17α-cyanomethyl estradiol methyl ether. Steroids 1980 (in press)
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Hillesheim, H.G., Göhler, P., Güttner, J. (1980). Different Pituitary Prolactin Cell-Stimulating Effects of Various Estrogens in Female Rats. In: Chambers, P.L., Klinger, W. (eds) Further Studies in the Assessment of Toxic Actions. Archives of Toxicology, vol 4. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-67729-8_107
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DOI: https://doi.org/10.1007/978-3-642-67729-8_107
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-10191-8
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