Proplatelet formation of megakaryocytes is triggered by autocrine-synthesized estradiol

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

研究成果: Article査読

79 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)2864-2869
ページ数6
ジャーナルGenes and Development
17
23
DOI
出版ステータスPublished - 2003 12 1
外部発表はい

ASJC Scopus subject areas

  • 遺伝学
  • 発生生物学

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