Combined effects of progesterone and tamoxifen in the chick oviduct.

Tamoxifen, an antiestrogen with no estrogenic effect on growth, differentiation, and egg white protein synthesis in the chick oviduct, has been administered together with progesterone. In estrogen differentiated, hormone-withdrawn animals, biochemical and ultrastructural data indicated that the combined treatment with progesterone plus tamoxifen increased conalbumin (+100%) and ovalbumin (+30%) more than progesterone alone and displayed estrogen-like growth-promoting properties (+50% in DNA content per oviduct). Moreover, when administered with progesterone and estradiol, tamoxifen lost part of its antiestrogenic activity. No obvious change of progesterone clearance from the blood or progesterone metabolism was recorded. The presence of progesterone in amounts similar to those resulting in optimal activity when injected alone (greater than or equal to 1 mg/kg) was necessary to obtain progesterone plus tamoxifen effects. The simultaneous presence of progesterone and tamoxifen was required in order to observe their combined effects, and it was observed that progesterone did not have to commit cells on which tamoxifen could subsequently act. In the immature "undifferentiated" oviduct, contrary to the effects of tamoxifen and progesterone alone, their combination induced cytodifferentiation of tubular gland cells which synthesized conalbumin and ovalbumin, an event never observed before in the absence of estrogen. These results support the suggestion that the hormonal milieu interferes with antiestrogen action.