Prolactin signaling through the short isoform of the mouse prolactin receptor regulates DNA binding of specific transcription factors, often with opposite effects in different reproductive issues.
BACKGROUND
It has been well established that prolactin (PRL) signals through the long form of its receptor (PRL-RL) and activates the Jak/Stat pathway for transcription of PRL target genes. However, signaling pathways mediated through the short PRL-R isoform (PRL-RS) remains controversial. Our recent finding that PRL signaling through PRL-RS represses two transcription factors critical for follicular development lead us to examine other putative PRL/PRL-RS target transcription factors in the decidua and ovary, two well-known target tissues of PRL action in reproduction.


METHODS
In this investigation we used mice expressing PRL-RS on a PRL-R knockout background and a combo protein/DNA array to study the transcription factors regulated by PRL through PRL-RS only.


RESULTS
We show that PRL activation of the PRL-RS receptor either stimulates or inhibits the DNA binding activity of a substantial number of transcription factors in the decidua as well as ovary. We found few transcription factors to be similarly regulated in both tissues, while most transcription factors are oppositely regulated by PRL in the decidua and ovary. In addition, some transcription factors are regulated by PRL only in the ovary or only in the decidua. Several of these transcription factors are involved in physiological pathways known to be regulated by PRL while others are novel.


CONCLUSIONS
Our results clearly indicate that PRL does signal through PRL-RS in the decidua as well as the ovary, independently of PRL-RL, and activates/represses transcription factors in a tissue specific manner. This is the first report showing PRL/PRL-RS regulation of specific transcription factors. Many of these transcription factors were not previously known to be PRL targets, suggesting novel physiological roles for this hormone.
Devi
Y Sangeeta
YS
Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Illinois 60612, USA. sangyen@uic.edu
Shehu
Aurora
A
Halperin
Julia
J
Stocco
Carlos
C
Le
Jamie
J
Seibold
Anita M
AM
Gibori
Geula
G
D000818:Animals; D000071616:CDX2 Transcription Factor; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D003656:Decidua / Q000187:drug effects* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011388:Prolactin / Q000008:administration & dosage / Q000494:pharmacology*; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D050676:Core Binding Factor Alpha 2 Subunit; D005136:Eye Proteins; D018398:Homeodomain Proteins; D051757:PAX5 Transcription Factor; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C497282:Pax5 protein, mouse; C000605732:Pax6 protein, mouse; D020033:Protein Isoforms; D011981:Receptors, Prolactin; D012097:Repressor Proteins; C493726:Runx1 protein, mouse; D014157:Transcription Factors; D011388:Prolactin; D004247:DNA
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