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Genes Dev. 2003 Dec 1;17(23):2864-9.

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

Author information

  • 1Recognition and Formation, Precursory Research for Embryonic Science and Technology, Japan Science and Technology Corporation, Japan. y-nagata@postman.riken.go.jp

Erratum in

  • Genes Dev. 2005 Aug 1;19(15):1823.

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, 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.

PMID:
14665668
PMCID:
PMC289146
DOI:
10.1101/gad.1128003
[PubMed - indexed for MEDLINE]
Free PMC Article
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