Regulation of prolactin production and cell growth by estradiol: difference in sensitivity to estradiol occurs at level of messenger ribonucleic acid accumulation.
17 beta-Estradiol increases the growth rate of GH4C1 cells with a half-maximally effective concentration (EC50) that is about 10-fold less than the EC50 for the stimulation of PRL production. We have examined the effects of five other estrogens: estriol, estrone, 17 alpha-estradiol, and the metabolism-resistant analogs ethynyl estradiol and moxestrol. All were full agonists for both effects, and all were more potent for the stimulation of cell growth than for stimulation of PRL production. The order of analog potency for both biological effects was the same as the order of potency for inhibiting saturable [3H]estradiol binding to intact cells. Therefore, both biological effects appear to be mediated through the same receptor, and metabolism of 17 beta-estradiol is unlikely to account for the difference in the concentrations required to elicit the two effects. We selected two estrogen-responsive clones from a cDNA library made from GH4C1 cells. The clones were chosen because they were induced at the estrogen concentrations that stimulate growth. Estradiol caused maximal stimulation of the mRNAs corresponding to the two recombinant clones at 10(-10) M, a concentration over 10-fold lower than that required for maximal stimulation of PRL mRNA. These data indicate that a difference in sensitivity to estrogen occurs at the level of mRNA accumulation as well as at the level of the biological responses.
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D011388:Prolactin / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism; D013329:Structure-Activity Relationship
D004967:Estrogens; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D004958:Estradiol; D011388:Prolactin