Proplatelet formation of megakaryocytes is triggered by autocrine-synthesized estradiol

Yuka Nagata, Jun Yoshikawa, Atsushi Hashimoto, Masayuki Yamamoto, Anita H. Payne, Kazuo Todokoro

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2864-2869
Number of pages6
JournalGenes and Development
Volume17
Issue number23
DOIs
Publication statusPublished - 2003 Dec 1

Keywords

  • 3β-HSD
  • Hematopoiesis
  • Proplatelet
  • Sex steroid hormone
  • p45 NF-E2

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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