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.
Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
S
S
Nishikawa
R C
RC
Moore
N
N
Nonomura
T
T
Oka
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