title: Mid-gestation ovine cardiomyocytes are vulnerable to mitotic suppression by thyroid hormone.
abstract: Circulating fetal 3,3',5-tri-iodo-l-thyronine (T(3) ) is maintained at very low levels until a dramatic prepartum surge. 3,3',5-Tri-iodo-l-thyronine inhibits serum-stimulated proliferation in near-term ovine cardiomyocytes, but it is not known whether midgestation myocytes are also inhibited. Because early cessation of cardiomyocyte mitosis would result in an underendowed heart, we hypothesized that 0.67 gestation (100 of 145 days gestation) ovine cardiomyocytes would be insensitive to suppressive growth effects of T(3) . These younger cardiomyocytes were grown with T(3) in 10% serum-enriched media for 24 hours. Physiological (0.37, 0.75, and 1.5 nmol/L) concentrations of T(3) dramatically suppressed mitotic activity in cardiomyocytes (P < .001). 3,3',5-Tri-iodo-l-thyronine stimulated phosphorylation of extracellular signal-regulated kinase and AKT (also known as Protein Kinase B [PKB]) signaling pathways. Nevertheless, the protein content of the cell cycle suppressor, p21, increased 2-fold (P < .05), and promoter, cyclin D1, decreased by 50%. Contrary to our hypothesis, elevated levels of T(3) powerfully inhibit proliferation of midgestation fetal cardiomyocytes. Thus, midgestation maternal hyperthyroidism might lead to an underendowed fetal myocardium.
authors.affiliation: Heart Research Center, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Natasha N
authors.initials: NN
authors.lastname: Chattergoon
authors.forename: Samantha
authors.initials: S
authors.lastname: Louey
authors.forename: Philip
authors.initials: P
authors.lastname: Stork
authors.forename: George D
authors.initials: GD
authors.lastname: Giraud
authors.forename: Kent L
authors.initials: KL
authors.lastname: Thornburg
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D005260:Female; D005318:Fetal Heart / Q000166:cytology*; D005865:Gestational Age; D008938:Mitosis / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects*; D011247:Pregnancy; D012756:Sheep / Q000196:embryology*; D015398:Signal Transduction / Q000187:drug effects; D013963:Thyroid Hormones / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D013963:Thyroid Hormones; D014284:Triiodothyronine; D019938:Cyclin D1