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. |