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1 Dip. Scienze Biologiche ed Ambientali, Benevento, Italy
2 Dip. Scienze Biologiche, Napoli, Italy
3 Dip. Scienze della Vita, Caserta, Italy
4 Dip. Scienze Biologiche ed Ambientali, Benevento, Italy; Benevento, Italy
5 Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands, United States
6 Dipartimento Scienze Biologiche ed Ambientali, Universita degli Studi del Sannio, Benevento, Italy
* To whom correspondence should be addressed. E-mail: moreno{at}unisannio.it.
Ageing is associated with changes in thyroid gland physiology. Age-related changes in the contribution of peripheral tissues to thyroid hormone serum levels have yet to be systematically assessed. Here, we investigated age-related alterations in the contributions of the liver and kidney to thyroid hormone homeostasis using 6, 12 and 24 months old male Wistar rats. A significant and progressive decline in plasma T4 occurred with age but T3 was decreased only at 24 months. This was associated with an unchanged protein level of the thyroid hormone transporter MCT8 in the kidney and with a decreased MCT8 level in the liver at 24 months. Hepatic type 1 deiodinase (D1) protein level and activity declined progressively with age. Renal D1 levels were decreased at both 12 and 24 months but D1 activity was decreased only at 24 months. In the liver, no changes occurred in thyroid hormone receptor (TR) TR
1, whereas a progressive increase in TR beta 1 occurred at both mRNA and total protein levels. In the kidney, both TR
1 and TR
1 mRNA and total protein levels were unchanged between 6 and 12 months but increased at 24 months. Interestingly, nuclear TR
1 levels were decreased in both liver and kidney at 12 and 24 months, whereas nuclear TRalpha1 levels were unchanged. Collectively, our data show differential age-related changes among hepatic and renal MCT8 and D1 and TR expressions, and they suggest that renal D1 activity is maintained with age to compensate for the decrease in hepatic T3 production.
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