Proplatelet formation of megakaryocytes is triggered by autocrine-synthesized estradiol
- Yuka Nagata1,2,5,
- Jun Yoshikawa2,
- Atsushi Hashimoto1,2,
- Masayuki Yamamoto3,
- Anita H. Payne4, and
- Kazuo Todokoro2,5
- 1 Recognition and Formation, Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Corporation (JST), Japan
- 2 Cell Fate Signaling Research Unit, RIKEN (The Institute of Physical and Chemical Research), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
- 3 Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba 305-8577, Japan
- 4 Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305-5317, USA
Abstract
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, 3β-hydroxysteroid dehydrogenase (3β-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 3β-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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Footnotes
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1128003.
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↵5 Corresponding authors. E-MAIL y-nagata{at}postman.riken.go.jp; FAX 81 48 462 4827. E-MAIL todokoro{at}postman.riken.go.jp; FAX 81 48 462 4827.
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- Accepted October 10, 2003.
- Received July 1, 2003.
- Cold Spring Harbor Laboratory Press
