Thyroid hormone drives fetal cardiomyocyte maturation

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Tri-iodo-L-thyronine (T 3) suppresses the proliferation of near-term serum-stimulated fetal ovine cardiomyocytes in vitro. Thus, we hypothesized that T 3is a major stimulant of cardiomyocyte maturation in vivo. We studied 3 groups of sheep fetuses on gestational days 125-130 (term ∼145 d): a T 3-infusion group, to mimic fetal term levels (plasma T 3 levels increased from ∼0.1 to ∼1.0 ng/ml; t 1/2∼24 h); a thyroidectomized group, to produce low thyroid hormone levels; and a vehicle-infusion group, to serve as intact controls. At 130 d of gestation, sections of left ventricular freewall were harvested, and the remaining myocardium was enzymatically dissociated. Proteins involved in cell cycle regulation (p21, cyclin D1), proliferation (ERK), and hypertrophy (mTOR) were measured in left ventricular tissue. Evidence that elevated T 3 augmented the maturation rate of cardiomyocytes included 14% increased width, 31% increase in binucleation, 39% reduction in proliferation, 150% reduction in cyclin D1 protein, and 500% increase in p21 protein. Increased expression of phospho-mTOR, ANP, and SERCA2a also suggests that T 3 promotes maturation and hypertrophy of fetal cardiomyocytes. Thyroidectomized fetuses had reduced cell cycle activity and binucleation. These findings support the hypothesis that T 3 is a prime driver of prenatal cardiomyocyte maturation.

Original languageEnglish (US)
Pages (from-to)397-408
Number of pages12
JournalFASEB Journal
Volume26
Issue number1
DOIs
StatePublished - Jan 2012

Fingerprint

Thyroid Hormones
Cardiac Myocytes
Cyclin D1
Cells
Thyronines
Proteins
Hypertrophy
Atrial Natriuretic Factor
Sheep
Cell Cycle
Fetus
Tissue
Plasmas
Myocardium
Pregnancy
Serum

Keywords

  • p21
  • Proliferation
  • Sheep fetus

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Thyroid hormone drives fetal cardiomyocyte maturation. / Chattergoon, Natasha; Giraud, George; Louey, Samantha; Stork, Philip; Fowden, Abigail L.; Thornburg, Kent.

In: FASEB Journal, Vol. 26, No. 1, 01.2012, p. 397-408.

Research output: Contribution to journalArticle

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