Thyroid hormone inhibits proliferation of fetal cardiac myocytes in vitro

Abstract

Thyroid hormone (T3) is a key regulator of fetal organ maturation. Premature elevations of thyroid hormone may lead to a ‘mature’ cardio-phenotype. Thyroid hormone will stimulate maturation of ovine fetal cardiomyocytes in culture by decreasing their proliferative capacity. Group 1 fetal cardiomyocytes (~135 days gestation) were incubated with T3 (1.5, 3, 10, and 100 nM) and bromodeoxyuridine (BrdU; 10 μM) for 24 and 48 h. Group 2 cardiomyocytes were cultured with T3 alone for later protein analysis of cell cycle regulators. At all concentrations, T3 decreased BrdU uptake fourfold in serum media (P<0.001 versus serum, n = 5). Following serum-free (SF) T3 treatment, BrdU uptake was inhibited when compared with serum (P<0.001 versus serum, n = 5). p21 expression increased threefold (P<0.05 versus serum free, n = 4) and cyclin D1 expression decreased twofold (P<0.05 versus serum, n = 4) in T3-treated cardiomyocytes. (1) T3 inhibits fetal cardiomyocyte proliferation, while (2) p21 protein levels increase, and (3) cyclin D1 levels decrease. Thus, T3 may be a potent regulator of cardiomyocyte proliferation and maturation in the late gestation fetus.