A physiological role for glucuronidated thyroid hormones: Preferential uptake by H9c2(2-1) myotubes

Abstract

Conjugation reactions are important pathways in the peripheral metabolism of thyroid hormones. Rat cardiac fibroblasts produce and secrete glucuronidated thyroxine (T4G) and 3,3 ,5-triiodothyronine (T3G). We here show that, compared to fibroblasts from other anatomical locations, the capacity of cardiofibroblasts to secrete T4G and T3G is highest. H9c2(2-1) myotubes, a model system for cardiomyocytes, take up T4G and T3G at a rate that is 10-15 times higher than that for the unconjugated thyroid hormones. T3 and T4, and their glucuronides, stimulate H9c2(2-1) myoblast-to-myotube differentiation. A substantial ␤-glucuronidase activity was measured in H9c2(2-1) myotubes, and this confers a deconjugating capacity to these cells, via which native thyroid hormones can be regenerated from glucuronidated precursors. This indicates that the stimulatory effects on myoblast differentiation are exerted by the native hormones. We suggest that glucuronidation represents a mechanism to uncouple local thyroid hormone action in the heart from that in other peripheral tissues and in the systemic circulation. This could represent a mechanism for the local fine-tuning of cardiac thyroid hormone action.

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

“…The interaction of thyroid hormone and contractile activity can be analyzed either by inhibiting spontaneous contractions (576) or by electrically stimulating the cells (575). The cell line H9C2, derived from rat embryonic heart tissue, is used as an alternative to primary cardiomyocyte cultures and various aspects of thyroidhormone action and metabolism have been studied in H9C2 cells (579)(580)(581). Although this cell line has retained a number of cardiomyocyte characteristics, it exhibits many of the key properties of skeletal muscle.…”

The Emerging Role of TRα1 in Cardiac Repair: Potential Therapeutic Implications

“…The implication of TR α 1 in cell differentiation is shown in embryonic myoblast cultures (H9c2), which is considered a suitable model to study cell differentiation. Maturation of H9c2 is TH dependent process [25, 26]. TR α 1 expression is increased in parallel with the intracellular T3 at the stage of cell differentiation and pharmacological inactivation of TR α 1 significantly delays cardiac myoblast maturation [27].…”

Low salinity acclimation and thyroid hormone metabolizing enzymes in gilthead seabream (Sparus auratus)

“…fibroblasts, but not myocytes, synthesize and secrete glucuronidated iodothyronine conjugates in vitro, and it was subsequently shown that cells from the embryonic rat heart ventricle cell line H9c2(2-1) preferentially take up glucuronidated T4 and T3 over the native, unconjugated hormones (van der Heide et al, 2007;van der Heide et al, 2002). These findings support the r of conjugating and deconjugating enzymes in the m odulation of horm one bioactivities in an endocrine or paracrine fashion.…”