In Vivo Interaction Between Steroidal Alkylating Agents and Oestrogen Receptors in Rabbit Uteri

Abstract

The binding of steroidal alkylating agents to specific tissue component is necessary for the selective distribution of these compounds to their target tissues. The in vivo interaction of Estracyt or NSC-112259 with oestrogen receptors may play an important role in their action mechanism.Both Estracyt and NSC-112259 which were administrated in vivo, gradually reduced the binding of [3H] oestradiol to cytoplasmic oestrogen receptor in rabbit uteri. From this, it was suggested that a negligible amount of oestradiol was released from these compounds and that the oestradiol moiety was useful as a carrier for the nitrogen mustard moiety. And it appeared that the synthesis of a new receptor protein was inhibited by the nitrogen mustard moiety, thereby causing a decrease in the cytoplasmic oestrogen receptor level.Estracyt and oestradiol mustard (NSC-112259), a single and double nitrogen mustard ester of oestradiol-17/3 (Fig. 1), have been used for the treatment of prostatic and mammary tumours. The selective distribution of these compounds in tumours and the reduction of toxicity have been reported (Wall et al. 1969;Carroll et al. 1972;Szendröi et al. 1973;Müntzing et al. 1974).From the report by Kirdani et al. (1975) that Estracyt affects the uptake of labelled oestradiol-17/3 (Oe2) or oestriol in the rat or dog prostate, it is prob¬ able that the binding of nitrogen mustard ester of Oeo to specific Oeo receptors may be necessary for the selective distribution of these compounds in target tissues. Moreover, the interaction between these compounds and the oestrogen