H. Hillesheim, P. Göhler, J. Güttner
1980
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Journal
Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement
Abstract
Four newly synthesized estra-1,3,5(10)-triene-derivatives, --3-methoxy-17 alpha-cyanomethyl-estra-1,3,5(10)-triene-17 beta-ol (I), --3-methoxy-17 alpha-rhodanomethyl-estra-1,3,5(10)-triene-17 beta-ol-tetrahydropyranylether (II), --17 beta-(N',N'-dimethylhydrazinocarbonyloxy)-estra-1,3,5(10)-triene-3-ol (III), --3-methoxy-17 beta-(N-phenylaminocarbonyloxy)-estra-1,3,5(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: 17 beta-hydroxy-17 alpha-alkylsubstituted derivatives (I, II, V) were less effective than 17 beta-carbamyloxy-derivatives (III, IV). These findings may be related to differences in pituitary accumulation of the investigated compounds, indicating any disposition-effect-relationships.