Inhibition by estradiol of the lactogenic effect of prolactin in primate mammary tissue: reversal by antiestrogens LY 156758 and tamoxifen.
Increasing concentrations of estradiol (E2) ranging from 0.01 to 10 nM were found to inhibit partially but significantly the lactogenic effect of ovine prolactin (oPRL) on alpha-lactalbumin production in primate mammary tissues maintained in organ culture for 9 days. E2 at 10 nM inhibited by 38% (mean) PRL-stimulated alpha-lactalbumin production measured by radioimmunoassay. E2 antagonized the effect of oPRL by reducing new alpha-lactalbumin synthesis as determined by specific immunoprecipitation of alpha-lactalbumin and by analysis with NaDodSO4 gel electrophoresis. In immunoprecipitation studies, the mean inhibition of alpha-lactalbumin production was 57.6%. E2 in the absence of oPRL had no effect on alpha-lactalbumin production. In contrast to previous observations in rodents, progesterone was found to be a much weaker inhibitor of PRL-induced alpha-lactalbumin production than was E2 in primate breast tissues. Mean inhibition of oPRL-stimulated alpha-lactalbumin production was 32.3% with 10 microM progesterone and 8.3% with 10 nM. The inhibitory effect of E2 on oPRL-stimulated alpha-lactalbumin production was significantly reversed by both tamoxifen and a new antiestrogen, LY 156758. Although exact comparison of the effects of these two antiestrogens was not possible, it was apparent that LY 156758 was more potent in blocking the E2 inhibitory effect. In summary, these studies provide evidence that physiologic concentrations of estradiol partially block the lactogenic effect of PRL in primate mammary glands, suggesting a new role for estrogen in mammary physiology. The inhibitory effect of estrogen treatment on milk production in women after parturition may possibly be explained by this direct antagonism between E2 and PRL.
D000818:Animals; D004336:Drug Antagonism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007768:Lactalbumin / Q000494:pharmacology; D007774:Lactation / Q000187:drug effects*; D008253:Macaca mulatta; D008254:Macaca nemestrina; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D010880:Piperidines / Q000494:pharmacology*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D011388:Prolactin / Q000494:pharmacology*; D020849:Raloxifene Hydrochloride; D013629:Tamoxifen / Q000494:pharmacology*
D010880:Piperidines; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride; D011374:Progesterone; D004958:Estradiol; D011388:Prolactin; D007768:Lactalbumin