TY - JOUR
T1 - Mid-gestation ovine cardiomyocytes are vulnerable to mitotic suppression by thyroid hormone
AU - Chattergoon, Natasha N.
AU - Louey, Samantha
AU - Stork, Philip
AU - Giraud, George D.
AU - Thornburg, Kent L.
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: supported by NIH grants NICHD P01 HD 34430 , NINDS R37, NS045737 , NHLBI R21 HL093617 , and R01 HL102763 ; NNC was supported by NHLBI training grant T32HL094294 and KLT was supported by the M. Lowell Edwards Endowment.
PY - 2012/6
Y1 - 2012/6
N2 - Circulating fetal 3,3′,5-tri-iodo-l-thyronine (T3) 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 T3. These younger cardiomyocytes were grown with T3 in 10% serum-enriched media for 24 hours. Physiological (0.37, 0.75, and 1.5 nmol/L) concentrations of T3 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 T3 powerfully inhibit proliferation of midgestation fetal cardiomyocytes. Thus, midgestation maternal hyperthyroidism might lead to an underendowed fetal myocardium.
AB - Circulating fetal 3,3′,5-tri-iodo-l-thyronine (T3) 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 T3. These younger cardiomyocytes were grown with T3 in 10% serum-enriched media for 24 hours. Physiological (0.37, 0.75, and 1.5 nmol/L) concentrations of T3 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 T3 powerfully inhibit proliferation of midgestation fetal cardiomyocytes. Thus, midgestation maternal hyperthyroidism might lead to an underendowed fetal myocardium.
KW - cardiomyocyte proliferation
KW - cyclin D1
KW - fetal heart
KW - p21
KW - thyroid hormone
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U2 - 10.1177/1933719111432860
DO - 10.1177/1933719111432860
M3 - Article
C2 - 22421446
AN - SCOPUS:84862892280
SN - 1933-7191
VL - 19
SP - 642
EP - 649
JO - Reproductive Sciences
JF - Reproductive Sciences
IS - 6
ER -