Research

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

Y Sangeeta Devi^1* , Aurora Shehu^1* , Julia Halperin^1,2 , Carlos Stocco¹ , Jamie Le¹ , Anita M Seibold¹ and Geula Gibori¹

¹  Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Illinois 60612, USA

²  Universidad Maimonides, Hidalgo 775 – C.P.: C1405BCK, Ciudad Autonoma de Buenos Aires, Argentina

author email corresponding author email* Contributed equally

Reproductive Biology and Endocrinology 2009, 7:87doi:10.1186/1477-7827-7-87

Published:	24 August 2009

Abstract

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.

Conclusion

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.