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This Article Full Text Full Text (PDF) All Versions of this Article: 294/6/E1160    most recent 00044.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Silvestri, E. Articles by Moreno, M. PubMed PubMed Citation Articles by Silvestri, E. Articles by Moreno, M.

Age-related changes in renal and hepatic cellular mechanisms associated with variations in rat serum thyroid hormone levels

¹Dipartimento di Scienze Biologiche ed Ambientali, Università degli Studi del Sannio, Benevento; ²Dipartimento delle Scienze Biologiche, Sezione Fisiologia, Università degli Studi di Napoli "Federico II", Naples; ³Dipartimento di Scienze della Vita, Seconda Università di Napoli, Caserta, Italy; and ⁴Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Submitted 23 January 2008 ; accepted in final form 21 April 2008

Aging 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-mo-old male Wistar rats. A significant and progressive decline in plasma thyroxine occurred with age, but triiodothyronine (T₃) was decreased only at 24 mo. This was associated with an unchanged protein level of the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) in the kidney and with a decreased MCT8 level in the liver at 24 mo. Hepatic type I deiodinase (D1) protein level and activity declined progressively with age. Renal D1 levels were decreased at both 12 and 24 mo but D1 activity was decreased only at 24 mo. In the liver, no changes occurred in thyroid hormone receptor (TR) TR₁, whereas a progressive increase in TRβ₁ occurred at both mRNA and total protein levels. In the kidney, both TR₁ and TRβ₁ mRNA and total protein levels were unchanged between 6 and 12 mo but increased at 24 mo. Interestingly, nuclear TRβ1 levels were decreased in both liver and kidney at 12 and 24 mo, whereas nuclear TR₁ 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.

aging; deiodinase; liver; kidney