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Nagata, Y. et al.

Nagata, Yoshikawa, Hashimoto, Yamamoto, Payne, Todokoro,

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

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.[1]

References

Proplatelet formation of megakaryocytes is triggered by autocrine-synthesized estradiol. Nagata, Y., Yoshikawa, J., Hashimoto, A., Yamamoto, M., Payne, A.H., Todokoro, K. Genes Dev. (2003) [Pubmed]

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