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Publication : Proplatelet formation of megakaryocytes is triggered by autocrine-synthesized estradiol.

First Author  Nagata Y Year  2003
Journal  Genes Dev Volume  17
Issue  23 Pages  2864-9
PubMed ID  14665668 Mgi Jnum  J:305412
Mgi Id  MGI:6708009 Doi  10.1101/gad.1128003
Citation  Nagata Y, et al. (2003) Proplatelet formation of megakaryocytes is triggered by autocrine-synthesized estradiol. Genes Dev 17(23):2864-9
abstractText  A matured megakaryocyte releases thousands of platelets through a drastic morphological change, proplatelet formation (PPF). The megakaryocyte/erythrocyte-specific transcription factor, p45 NF-E2, is essential for initiating PPF, but the factor regulating PPF has not been identified. Here we report that estradiol synthesized in megakaryocytes triggers PPF. We demonstrate that a key enzyme for steroid hormone biosynthesis, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), is a target of p45 NF-E2, and rescues PPF of p45 NF-E2-deficient megakaryocytes. We also show that estradiol is synthesized within megakaryocytes, and that extracellular estradiol stimulates PPF, inhibition of 3beta-HSD activity blocks PPF, and estrogen receptor antagonists inhibit platelet production in vivo. We conclude that autocrine estradiol action regulates platelet production by triggering PPF.
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