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 17beta-estradiol, strong enhancement of [3H]leucine incorporation into prolactin an stimulation of translatable preprolactin mRNA, respectively, were noted. Increase in prolactin synthesis was found following daily application with estriol and the synthetic estrogen 1,3-dibenzoyloxy-17 beta-methyl-1,3,5(10)-estratrien-17 beta-ol (DB-EE2). The antiestrogen tamoxifen (trans-1-(p-beta-dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene) was demonstrated to inhibit estradiol-stimulated prolactin syntheses. Antagonistic effects of tamoxifen were dose dependent. Low loses of the antiestrogen were already sufficient to suppress 17 beta-estradiol-enhanced levels of prolactin mRNA. On the other hand, estriol potentiated 17 beta-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.
D000818:Animals; D002369:Castration; D002474:Cell-Free System; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000096:biosynthesis* / Q000097:blood; D011498:Protein Precursors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013629:Tamoxifen / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D011498:Protein Precursors; D012333:RNA, Messenger; D013629:Tamoxifen; D004958:Estradiol; C017671:preprolactin; D011388:Prolactin