Evidence for hormonal control of heart regenerative capacity during endothermy acquisition

Kentaro Hirose, Alexander Y. Payumo, Stephen Cutie, Alison Hoang, Hao Zhang, Romain Guyot, Dominic Lunn, Rachel B. Bigley, Hongyao Yu, Jiajia Wang, Megan Smith, Ellen Gillett, Sandra E. Muroy, Tobias Schmid, Emily Wilson, Kenneth A. Field, Dee Ann M. Reeder, Malcom Maden, Michael M. Yartsev, Michael J. WolfgangFrank Grützner, Thomas S. Scanlan, Luke I. Szweda, Rochelle Buffenstein, Guang Hu, Frederic Flamant, Jeffrey E. Olgin, Guo N. Huang

Research output: Contribution to journalArticlepeer-review

224 Scopus citations


Tissue regenerative potential displays striking divergence across phylogeny and ontogeny, but the underlying mechanisms remain enigmatic. Loss of mammalian cardiac regenerative potential correlates with cardiomyocyte cell-cycle arrest and polyploidization as well as the development of postnatal endothermy. We reveal that diploid cardiomyocyte abundance across 41 species conforms to Kleiber's law-the 3/4-power law scaling of metabolism with bodyweight-and inversely correlates with standard metabolic rate, body temperature, and serum thyroxine level. Inactivation of thyroid hormone signaling reduces mouse cardiomyocyte polyploidization, delays cell-cycle exit, and retains cardiac regenerative potential in adults. Conversely, exogenous thyroid hormones inhibit zebrafish heart regeneration. Thus, our findings suggest that loss of heart regenerative capacity in adult mammals is triggered by increasing thyroid hormones and may be a trade-off for the acquisition of endothermy.

Original languageEnglish (US)
Pages (from-to)184-188
Number of pages5
Issue number6436
StatePublished - 2019

ASJC Scopus subject areas

  • General


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