Progesterone and EGF inhibit mouse mammary gland prolactin receptor and beta-casein gene expression.
Regulation of mouse mammary gland long-form prolactin receptor (PRL-RL) mRNA levels by progesterone and epidermal growth factor (EGF) and the relationship between PRL-RL and beta-casein gene expression were examined in vivo and in vitro. PRL-RL and beta-casein mRNA levels increased approximately 6- and 15-fold from the pregnant to the lactating period, respectively, when normalized to the level of beta-actin mRNA. Ovariectomy of pregnant mice rapidly reduced the serum concentration of progesterone and increased the level of PRL-RL and beta-casein mRNAs approximately three- and fourfold compared with sham-operated animals 24 h after the operation. Injection of progesterone, but not estrogen, inhibited the increase in both mRNA levels. PRL-RL and beta-casein mRNA levels in cultured mammary epithelium increased in response to insulin, hydrocortisone, and prolactin, whereas progesterone or EGF caused inhibition. The combination of EGF and progesterone produced a greater inhibition than either hormone alone. These results indicate that both progesterone and EGF serve as negative regulators of lactogenesis.
Nishikawa
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Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Moore
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RC
Nonomura
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N
Oka
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T
D000818:Animals; D001483:Base Sequence; D002364:Caseins / Q000235:genetics*; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D007774:Lactation / Q000502:physiology; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D010052:Ovariectomy; D011247:Pregnancy; D011374:Progesterone / Q000097:blood / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011981:Receptors, Prolactin / Q000235:genetics*
D002364:Caseins; D015335:Molecular Probes; D012333:RNA, Messenger; D011981:Receptors, Prolactin; D011374:Progesterone; D004815:Epidermal Growth Factor