REGULATION OF A UTERINE 250 KDA PROTEIN BY ESTRADIOL AND ANTIESTROGENS

A 250 kDa secretory protein was isolated from the uterine luminal flui d (ULF) obtained from estradiol-treated ovariectomized rats. Antiestro gens blocked the production of this protein. The protein components we re separated and purified by SDS-PAGE. Polyclonal antibodies were rais ed against the 250 kDa protein and used to identify the protein by Wes tern blot. 17 beta-estradiol (E(2)) at a dose of 0.005 mg/kg/d adminis tered sc for 3 days to ovariectomized rats stimulated a marked increas e in the production of the 250 kDa protein. Anordiol at a low dose of 5 mg/kg/d x 3 po or 0.25 mg/kg/d x 3 sc stimulated the production of t he 250 kDa protein. Treatment with higher doses (10 mg/kg/d x 3 po, or 1.25 mg/kg/d x 3 sc) was less effective in inducing production of thi s protein. Also anordiol partially inhibited the stimulatory action of E(2); whereas ICI 182,780, a pure antiestrogen, at a dose of 0.3 mg/k g/d x 3 sc completely blocked the stimulatory action of E(2). The 250 kDa protein was not detected in the blood obtained from E(2)-treated o variectomized rats. The anti-complement C3 and anti-alpha(2)-macroglob ulin antibodies did not react with the ULF 250 kDa protein. The presen t results show that the production of the ULF 250 kDa protein is regul ated by estradiol and is not a component of blood plasma. It is propos ed that the estrogen-responsive 250 kDa protein may be involved in mai ntaining the viability of the fertilized ova and in the implantation o f the blastocyst.