Clusterin is a heterodimeric, 80kDa, glycoprotein that is synthesized in a wide variety of tissues in response to a number of diverse stimuli, including hormone ablation. We have investigated the regulation of clusterin expression by estradiol and anti-estrogens in RUCA-I rat endometrial adenocarcinoma cells in vitro and in vivo. We have also compared clusterin expression in endometrial tumors and in normal uterine tissue. Estradiol treatment significantly increases the steady state mRNA levels of clusterin in RUCA-I cells cultured on a reconstituted basement membrane, with a maximal induction 24 hr after estradiol treatment. The inductive effects of estrogen on clusterin mRNA steady state levels in vitro are significantly more pronounced than the effects on fibronectin mRNA levels, an estrogen-repressed gene in RUCA-I. In vivo, induction of clusterin expression in primary and metastatic endometrial adenocarcinoma is also dependent on the presence of estradiol, in marked contrast to expression of clusterin in the normal endometrium of the same animals. These data suggest that clusterin mRNA expression in rat endometrial adenocarcinoma cells is tightly regulated by estrogens and anti-estrogens in vitro and in vivo, and that there is a complex mechanism of regulation of clusterin expression in the normal and cancerous endometrium.