Inhibition by tamoxifen of estrogen-stimulated accumulation of preprolactin messenger ribonucleic acid

Estrogens are involved in the stimulation of prolactin synthesis in the rat anterior pituitary. After 5 days of treatment with 17β-estradiol, strong enhancement of [³H]leucine incorporation into prolactin and stimulation of translatable preprolactin mRNA, respectively, were noted. Increase in prolactin synthesis was also found following daily application with estriol and the synthetic estrogen 1,3-dibenzoyloxy-17β-methyl-1,3,5(10)-estratrien-17β-ol (DB-EE2). The antiestrogen tamoxifen (trans-1-(p-β-dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene) was demonstrated to inhibit estradiol-stimulated prolactin synthesis. Antagonistic effects of tamoxifen were dose dependent. Low doses of the antiestrogen were already sufficient to suppress 17β-estradiol-enhanced levels of prolactin mRNA. On the other hand, estriol potentiated 17β-estradiol-stimulated levels of serum prolactin and prolactin synthesis. Our results add further information about the transcriptional control by estrogens and demonstrate inhibitory actions of antiestrogens on distinct regulatory levels of protein synthesis in the rat pituitary.