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The rat Harderian gland (HG) is an orbital gland producing a copious lipid secretion. Recent studies indicate that its secretory activity is regulated by thyroid hormones. In this study, we found that both isoforms of the thyroid hormone receptor ( Tr  α  ( Thra ) and  Tr  β  ( Thrb )) are expressed in rat HGs. Although  Thra  is expressed at a higher level, only  Thrb  is regulated by triiodothyronine (T 3 ). Because T 3  induces an increase in lipid metabolism in rat HGs, we investigated the effects of an animal's thyroid state on the expression levels of carnitine palmitoyltransferase-1A ( Cpt1a ) and carnitine palmitoyltransferase-1B ( Cpt1b ) and acyl-CoA oxidase ( Acox1 ) (rate-limiting enzymes in mitochondrial and peroxisomal fatty acid oxidation respectively), as well as on the mitochondrial compartment, thereby correlating mitochondrial activity and biogenesis with morphological analysis. We found that hypothyroidism decreased the expression of  Cpt1b  and  Acox1  mRNA, whereas the administration of T 3  to hypothyroid rats increased transcript levels. Respiratory parameters and catalase protein levels provided further evidence that T 3  modulates mitochondrial and peroxisomal activities. Furthermore, in hypothyroid rat HGs, the mitochondrial number and their total area decreased with respect to the controls, whereas the average area of the individual mitochondrion did not change. However, the average area of the individual mitochondrion was reduced by ∼50% in hypothyroid T 3 -treated HGs, and the mitochondrial number and the total area of the mitochondrial compartment increased. The mitochondrial morphometric data correlated well with the molecular results. Indeed, hypothyroid status did not modify the expression of mitochondrial biogenesis genes such as  Ppargc1a ,  Nrf1  and  Tfam , whereas T 3  treatment increased the expression level of these genes.

Triiodothyronine induces lipid oxidation and mitochondrial biogenesis in rat Harderian gland