Effect of Tamoxifen on Oestradiol and Progesterone‐Induced Synthesis of Ovalbumin and Conalbumin in Chick Oviduct

Tamoxifen, a non-steroidal antioestrogen, did not display any oestrogenic effects biochemically or histologically in the chick oviduct when 10 mg/kg were administered to oestrogen-withdrawn animals each day and effects were monitored during periods ranging from a few hours to 10 days. After a single injection of oestradiol benzoate, 1 mg/kg, to oestrogen-withdrawn animals, the relative rate of ovalbumin synthesis was significantly elevated by 3 h, and reached a maximum by ∼ 16 h. Conalbumin synthesis increased immediately after oestrogen administration, and attained a maximum by ∼ 16 h. Between 16 and 24 h there was a decrease of ∼ 50% in the rate of synthesis of the two proteins and in the levels of nuclear oestrogen receptor. Administration of tamoxifen together with oestradiol benzoate inhibited the oestrogen effect on ovalbumin and conalbumin synthesis. This effect of tamoxifen was dose-dependent; 50% inhibition of the maximum induction of both proteins was obtained with 1 mg of tamoxifen/kg. A series of experiments indicated that tamoxifen given after oestradiol benzoate could rapidly inhibit the oestrogenic effect, and oestradiol benzoate administered subsequent to tamoxifen could overcome the antioestrogenic effect; that is, each ligand could produce its own characteristic activity, although in both cases, at the time of administration of the second drug, the level of cytoplasmic oestrogen receptor was low. When tamoxifen was administered during the lag period of ovalbumin induction, it decreased the entire pattern of ovalbumin synthesis, but when given later, the inhibitory effect was retarded. On the other hand, the inhibition by tamoxifen of oestradiol-dependent conalbumin synthesis was virtually immediate. The basal level of conalbumin synthesis, already significant in withdrawn chickens (1%), was unaffected by tamoxifen, suggesting that endogenous oestrogens are not required to maintain this level of synthesis. Progesterone-induced increases in ovalbumin and conalbumin synthesis were not inhibited by tamoxifen. On the contrary, the simultaneous injection of tamoxifen potentiated the progesterone-increased synthesis of both proteins. These observations were supported by histological studies showing an increased accumulation of secretory granules in the magnum of chickens treated by tamoxifen plus progesterone as compared to progesterone alone.