ABSTRACT
We investigated the effect of thyroid hormone (TH) receptor (TR)alpha and -beta isoforms in TH action in the heart. Noninvasive echocardiographic measurements were made in mice homozygous for disruption of TRalpha (TRalpha(0/0)) or TRbeta (TRbeta(-/-)). Mice were studied at baseline, 4 wk after TH deprivation (using a low-iodine diet containing propylthiouracil), and after 4-wk treatment with TH. Baseline heart rates (HR) were similar in wild-type (WT) and TRalpha(0/0) mice but were greater in TRbeta(-/-) mice. With TH deprivation, HR decreased 49% in WT and 37% in TRbeta(-/-) mice and decreased only 5% in TRalpha(0/0) mice from baseline, whereas HR increased in all genotypes with TH treatment. Cardiac output (CO) and cardiac index (CI) in WT mice decreased (-31 and -32%, respectively) with TH deprivation and increased (+69 and +35%, respectively) with TH treatment. The effects of CO and CI were blunted with TH withdrawal in both TRalpha(0/0) (+8 and -2%, respectively) and TRbeta(-/-) mice (-17 and -18%, respectively). Treatment with TH resulted in a 64% increase in LV mass in WT and a 44% increase in TRalpha(0/0) mice but only a 6% increase in TRbeta(-/-) mice (ANOVA P < 0.05). Taken together, these data suggest that TRalpha and TRbeta play different roles in the physiology of TH action on the heart.
Subject(s)
Heart/physiology , Receptors, Thyroid Hormone/physiology , Thyroid Hormones/physiology , Animals , Body Weight , Echocardiography , Heart Rate/physiology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout/genetics , Receptors, Thyroid Hormone/deficiency , Receptors, Thyroid Hormone/genetics , Thyroid Function Tests , Thyroid Hormone Receptors betaABSTRACT
The house musk shrew Suncus murinus (Insectivora: Soricidae) has been reported as having low thyroxine to 3,3'5-triiodothyronine (T(3)) converting activity in liver and kidney homogenates and was assumed to be type 1 iodothyronine deiodinase (D1)-deficient. To study whether this is due to structural abnormality of shrew D1, we cloned the cDNA and characterized the enzyme. The deduced amino acid sequence of shrew D1 was found to be highly homologous to other known D1s and the enzyme itself to have similar catalytic activity. However, unlike in other species, the D1 activity was detected only in liver. Moreover, the D1 activity in liver of the shrew was less than half of that in rat liver and its expression was not up-regulated by T(3). In contrast, a very high activity of D2 was demonstrated in brain and brown adipose tissue. The present study also revealed that the serum level of T(3) in the shrew was in the same range as these in other mammals. These results suggest that D2 contributes to the production and maintenance of T(3) levels in the house musk shrew.
