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Mid-Gestation Ovine Cardiomyocytes Are Vulnerable to Mitotic Suppression by Thyroid Hormone

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Abstract

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.

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Authors and Affiliations

  1. Heart Research Center, Oregon Health & Science University, 3303 SW Bond Ave, CH15H, Portland, OR, 97239, USA

    Natasha N. Chattergoon PhD, Samantha Louey PhD, Philip Stork MD, George D. Giraud MD, PhD & Kent L. Thornburg PhD

  2. Department of Medicine (Cardiovascular Medicine), Oregon Health & Science University, Portland, OR, USA

    Samantha Louey PhD, George D. Giraud MD, PhD & Kent L. Thornburg PhD

  3. Vollum Institute for Advanced Biomedical Research, Oregon Health & Science University, Portland, OR, USA

    Philip Stork MD

  4. Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR, USA

    George D. Giraud MD, PhD & Kent L. Thornburg PhD

  5. Cardiology, Portland Veterans Affairs Medical Center, Portland, OR, USA

    George D. Giraud MD, PhD

Authors
  1. Natasha N. Chattergoon PhD
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  2. Samantha Louey PhD
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  3. Philip Stork MD
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  4. George D. Giraud MD, PhD
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  5. Kent L. Thornburg PhD
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Correspondence to Kent L. Thornburg PhD.

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Chattergoon, N.N., Louey, S., Stork, P. et al. Mid-Gestation Ovine Cardiomyocytes Are Vulnerable to Mitotic Suppression by Thyroid Hormone. Reprod. Sci. 19, 642–649 (2012). https://doi.org/10.1177/1933719111432860

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  • DOI: https://doi.org/10.1177/1933719111432860

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