INVESTIGADORES
HALPERIN Julia
congresos y reuniones científicas
Título:
Prolactin (PRL) is critical for maintenance of pregnancy in the rodents
Autor/es:
SHEHU A, SANGEETA Y, HALPERIN J, HERETIS K, AND GIBORI G
Lugar:
New London, USA
Reunión:
Conferencia; Gordon Research Conference in Reproductive Tract Biology; 2006
Institución organizadora:
Gordon Research Conferences (GRC)
Resumen:
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Prolactin is critical for maintenance of pregnancy in rodents. This isdue 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 theluteal defect is compensated by injection of progesterone. We have shown thatPRL is produced in the decidua of the rat and mouse and in rodents thisdecidual PRL acts locally to inhibit the expression of genes detrimental topregnancy, such as IL-6, 20aHSD and activin A. PRL bind to two type ofreceptors yet the signaling mechanism through the short form(PRL-RS) has notbeen identified. This investigation was undertaken to gain insight into thesignal transduction pathways activated by PRL in the decidua acting onlythrough PRL-RS. We used PRLR null mice overexpressing PRL-RS and atranscription reporter array with consensus binding sequences for 354 transcriptionfactors (TFs).PRL-RS transgene female mice were mated with vasectomized malesto initiate pseudopregnancy. PRL was administered and decidual tissue wascollected 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 thepresence 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 amarked increase in DNA binding activity of TFs (Pax5, Pax8, GATA1, AP3, AP4,PEBP1, PEBP2, TEF1, CREB2, Fast1, Cdx2, NF-Y), which remained activated 120minlater. In our model, upon PRL treatment MAPK phosphorylation was drasticallydecreased in both the decidua and the ovary. In addition, PRL inhibited DNA bindingactivity of transcriptional factors downstream of MAPK and other kinases (AP1,AP2, SP1, COUP-TF). Several of the transcription factors (NF-1, AP2) stimulatedby PRL in this analysis have been previously shown to mediate PRL signaling inother tissues, while others are potentially novel mediators of PRL effects.EMSA and western blot analysis substantiate microarray results fortranscription factors investigated. In summary, our results have revealed, forthe first time, that PRL produced by decidua can indeed signal through theshort form of its receptor by either activating or inhibiting the activity ofseveral transcription factors. Supported by NIH HD12356, U54HD40093 and APS
