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:
Chicago, USA
Reunión:
Simposio; 20th Chicago Signal Transduction Symposium; 2007
Institución organizadora:
Northwestern University
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:Times;
panose-1:2 2 6 3 5 4 5 2 3 4;
mso-font-charset:0;
mso-generic-font-family:roman;
mso-font-pitch:variable;
mso-font-signature:536902279 -2147483648 8 0 511 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;
mso-bidi-font-size:10.0pt;
font-family:"Times","serif";
mso-fareast-font-family:Times;
mso-bidi-font-family:"Times New Roman";}
pre
{mso-style-unhide:no;
mso-style-link:"HTML Preformatted Char";
margin:0in;
margin-bottom:.0001pt;
mso-pagination:widow-orphan;
font-size:10.0pt;
font-family:"Courier New";
mso-fareast-font-family:"Times New Roman";
color:black;}
span.HTMLPreformattedChar
{mso-style-name:"HTML Preformatted Char";
mso-style-unhide:no;
mso-style-locked:yes;
mso-style-link:"HTML Preformatted";
font-family:"Courier New";
mso-ascii-font-family:"Courier New";
mso-fareast-font-family:"Times New Roman";
mso-hansi-font-family:"Courier New";
mso-bidi-font-family:"Courier New";
color:black;}
.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:Times;
mso-fareast-font-family:Times;
mso-hansi-font-family:Times;}
@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;}
-->
<!--
/* 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;}
@font-face
{font-family:Gisha;
panose-1:2 11 5 2 4 2 4 2 2 3;
mso-font-charset:0;
mso-generic-font-family:swiss;
mso-font-pitch:variable;
mso-font-signature:-2147481593 1073741890 0 0 33 0;}
/* Style Definitions */
p.MsoNormal, li.MsoNormal, div.MsoNormal
{mso-style-unhide:no;
mso-style-qformat:yes;
mso-style-parent:"";
margin-top:0in;
margin-right:0in;
margin-bottom:10.0pt;
margin-left:0in;
line-height:115%;
mso-pagination:widow-orphan;
font-size:11.0pt;
font-family:"Calibri","sans-serif";
mso-fareast-font-family:Calibri;
mso-bidi-font-family:"Times New Roman";
mso-ansi-language:ES-AR;}
.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;}
-->
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 120min
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