INVESTIGADORES
HALPERIN Julia
congresos y reuniones científicas
Título:
Prolactin signals through the short form of its cognate receptor in the decidua
Autor/es:
AURORA SHEHU, SANGEETA DEVI, KONSTANTINA HERETIS, JULIA HALPERIN, NADINE BINART AND GEULA GIBORI.
Lugar:
Omaha, USA
Reunión:
Congreso; Society for Study of Reproduction 39th Annual Meeting; 2006
Institución organizadora:
Society for Study of Reproduction (SSR)
Resumen:
<!--
/* Font Definitions */
@font-face
{font-family:"Cambria Math";
panose-1:2 4 5 3 5 4 6 3 2 4;
mso-font-charset:0;
mso-generic-font-family:roman;
mso-font-pitch:variable;
mso-font-signature:-1610611985 1107304683 0 0 159 0;}
@font-face
{font-family:Calibri;
panose-1:2 15 5 2 2 2 4 3 2 4;
mso-font-charset:0;
mso-generic-font-family:swiss;
mso-font-pitch:variable;
mso-font-signature:-1610611985 1073750139 0 0 159 0;}
/* Style Definitions */
p.MsoNormal, li.MsoNormal, div.MsoNormal
{mso-style-unhide:no;
mso-style-qformat:yes;
mso-style-parent:"";
margin:0in;
margin-bottom:.0001pt;
mso-pagination:widow-orphan;
font-size:12.0pt;
font-family:"Times New Roman","serif";
mso-fareast-font-family:"Times New Roman";}
.MsoChpDefault
{mso-style-type:export-only;
mso-default-props:yes;
font-size:10.0pt;
mso-ansi-font-size:10.0pt;
mso-bidi-font-size:10.0pt;
mso-ascii-font-family:Calibri;
mso-fareast-font-family:Calibri;
mso-hansi-font-family:Calibri;}
@page Section1
{size:8.5in 11.0in;
margin:1.0in 1.0in 1.0in 1.0in;
mso-header-margin:.5in;
mso-footer-margin:.5in;
mso-paper-source:0;}
div.Section1
{page:Section1;}
-->
Prolactin
(PRL) is critical for maintenance of pregnancy in the rodents. This is due in
part to its role in the development and function of the corpus luteum. However,
mice lacking a functional PRL gene abort at midpregnancy even if the luteal
defect is compensated by injection of progesterone. We have shown that PRL is
produced in the decidua of the rat and mouse and in rodents this decidual PRL
acts locally to inhibit the expression of genes detrimental to pregnancy, such
as IL-6, 20aHSD and activin A. PRL bind to two type of receptors yet the
signaling mechanism through the short form(PRL-RS) has not been identified.
This investigation was undertaken to gain insight into the signal transduction pathways
activated by PRL in the decidua acting only through PRL-RS. We used PRLR null
mice overexpressing PRL-RS and a transcription reporter array with consensus
binding sequences for 354 transcription factors (TFs). PRL-RS transgene female
mice were mated with vasectomized males to initiate pseudopregnancy. PRL was
administered and decidual tissue was collected after 0, 30, or 120 minutes. Of
the 345 TFs present in the array, 104 (30%) were detectable in nuclear extracts
of decidual tissue. In the presence of PRL treatment, many TFs from several
families such as Pax, GATA, and AP were found to be stimulated or inhibited.
Within 30 min PRL induced a marked increase in DNA binding activity of TFs
(Pax5, Pax8, GATA1, AP3, AP4, PEBP1, PEBP2, TEF1, CREB2, Fast1, Cdx2, NF-Y),
which remained activated 120 min later. In our model, upon PRL treatment MAPK
phosphorylation was drastically decreased in both the decidua and the ovary. In
addition, PRL inhibited DNA binding activity of transcriptional factors
downstream of MAPK and other kinases (AP1, AP2, SP1, COUP-TF). Several of the
transcription factors (NF-1, AP2) stimulated by PRL in this analysis have been
previously shown to mediate PRL signaling in other tissues, while others are
potentially novel mediators of PRL effects. EMSA and western blot analysis
substantiate microarray results for transcription factors investigated. In
summary, our results have revealed, for the first time, that PRL produced by
decidua can indeed signal through the short form of its receptor by either
activating or inhibiting the activity of several transcription factors. Supported
by NIH HD12356, U54HD40093 and APS.
