Thyroid hormone inhibits proliferation of fetal cardiac myocytes in vitro.
Thyroid hormone (T(3)) 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 (approximately 135 days gestation) were incubated with T3 (1.5, 3, 10, and 100 nM) and bromodeoxyuridine (BrdU; 10 microM) 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.
Chattergoon
N N
NN
Heart Research Center, Oregon Health and Science University, Portland, Oregon 97239-3098, USA. chatterg@ohsu.edu
Giraud
G D
GD
Thornburg
K L
KL
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000032:analysis / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis / Q000378:metabolism; D003864:Depression, Chemical; D005260:Female; D006321:Heart / Q000196:embryology*; D007150:Immunohistochemistry; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D012756:Sheep; D014284:Triiodothyronine / Q000494:pharmacology*
D015415:Biomarkers; D050759:Cyclin-Dependent Kinase Inhibitor p21; D014284:Triiodothyronine; D019938:Cyclin D1; D001973:Bromodeoxyuridine