Developmental regulation of murine mammary progesterone receptor gene expression.
Previously we have shown that in normal murine mammary glands progesterone receptor (PgR) levels are modulated as a function of development and differentiation such that lactating mammary glands do not contain detectable levels of PgR as measured by steroid binding. The objective of the present study was to determine whether the lack of steroid binding in lactating mammary glands was due to the absence of receptor protein and if so whether it was accompanied by an alternation in the pattern of PgR gene expression. Accordingly, we have performed an immunological analysis of murine mammary PgR isolated from different developmental states and have also examined these tissues for PgR gene expression. In mammary tissues from all developmental states other than lactation, immunoreactive PgR corresponding to both A and B forms of the protein were detected. Analysis for PgR mRNA revealed multiple species in mammary tissues and the relative order of abundance of the various transcripts and their sizes were approximately 6.9 greater than 8.7 greater than 3.5 greater than 2.7 greater than 4.2. The 6.9 and 8.7 kilobase transcripts accounted for between 70-80% of total mRNA. All five species of mRNA were detected in tissues from nulliparous mice which decreased dramatically during pregnancy, became undetectable during lactation, and were once again detectable in tissues from mice undergoing lactational involution. Experiments designed specifically to examine the effect of estradiol on mammary PgR mRNA revealed that in contrast to tissues from other developmental states, lactating mammary glands were unable to respond to estradiol with an increase in PgR mRNA. Based on these findings and the fact that estrogenic insensitivity of lactating mammary glands coexists with the presence of ER we propose that in this tissue there is an alteration in the estrogen dependent transcriptional regulation of PgR gene expression.
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada.
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Shyamala
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Schneider
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D000345:Affinity Labels; D000818:Animals; D015153:Blotting, Western; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D007163:Immunosorbent Techniques; D007774:Lactation / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010777:Photochemistry; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics*
D000345:Affinity Labels; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D004958:Estradiol