Estrogen interaction with the anterior pituitary of female rats differential cytosol binding, nuclear translocation and stimulation of RNA synthesis by 17β-estradiol and tamoxifen

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The interaction of tamoxifen ( trans-1-( p- β-dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene) with the cytosol estrogen receptor of the anterior pituitary of female rats was studied. No differences were recorded between incubations of cytosol samples with 17β-[ 3H]estradiol performed in the presence or absence of unlabeled 17β-estradiol and tamoxifen, respectively, thus suggesting that these interactions were at common receptor sites and excluding possible cooperative interactions. Competition experiments and Scatchard plot analysis of saturation experiments add further evidence for common receptor sites. A dissociation constant for tamoxifen of K d = 2 nM was recorded. Tamoxifen was found to be bound to a moiety sedimenting in the 4–5 S region, on a 6–24% linear sucrose density gradient at low salt concentrations, whereas 17β-estradiol sedimented in the 8–9 S area. These data suggest possible conformational changes of the receptor in the presence of tamoxifen. Furthermore, nuclear estrogen receptor levels remained elevated for at least 80 h after the application of tamoxifen alone or in a combination with 17β-estradiol, and a concomitant inhibition of cytosol receptor replenishment was noted. Tamoxifen and 17β-estradiol, respectively, were found to stimulate progesterone receptor levels when applied through 5 days. Tamoxifen plus 17β-estradiol administration elevated progesterone receptor contents above those found for each of the two compounds alone. On the other hand, tamoxifen enhanced the 17β-estradiol-induced prolactin serum levels, but did not stimulate prolactin serum levels by itself. These data combine to suggest that tamoxifen interacts with common estrogen receptor sites at the rat anterior pituitary.