Modulation of Type 2 Iodothyronine Deiodinase Activity in Rat Thyroid Gland

Introduction

The majority of biological responses to thyroid hormones require the enzymatic conversion of thyroxine (T4) to triiodothyronine (T3), the bioactive hormone. Two distinct enzymes are responsible for this reaction, namely type 1 and 2 iodothyronine deiodinases (D1 and D2). Based on several functional criteria, D1 and D2 have major kinetic differences and distinct tissue distribution. According to current concepts, D1 and D2 have similar contribution to plasma T3 generation [1].

Thyroid gland has a very high D1 activity and the presence of D2 activity and mRNA expression in both human [1] [2] [3] [4] and rat [5] [6] [7] [8] thyroids have been detected. Although in humans most T3 has extrathyroidal origin, in rats, the thyroid gland contributes with approximately 50% of serum T3 [9], coming not only from the thyroid production but also from intrathyroidal T4 to T3 conversion, catalyzed predominantly by D1. Therefore, the modulation of thyroid deiodination process may have consequences to plasma T3 production in rodents. The stimulatory role of TSH upon thyroid D1 has been well described [1], but there are only few data about the regulation of thyroid deiodination, mainly concerning D2 activity.

In human thyroid, D2 mRNA was found at higher level than in placenta and it was especially high in Graves’ patients and in follicular adenomas, suggesting that intrathyroidal T4 to T3 conversion by D2 contributes to elevate thyroid T3 production [4]. In avian species, D2 is expressed in thyroid in the same level as in brain [10]. We have previously detected [7] that in rats, TSH seems to upregulate D2, as well as D1, since hypothyroidism was associated with high thyroid D2 and D1 activity. However, both thyroid deiodinase activities were decreased in rats submitted to cold exposure for a short period, despite high TSH levels. Leptin modulates thyroid deiodination by increasing D1 activity, but was not able to change D2 activity [7].

Here we studied the response of thyroid D2 activity, and in parallel that of D1, to sexual dimorphism, gonadectomy, fasting, and diabetes mellitus, since in rodents, the thyroid is very important for generating serum T3 and very little is known about thyroid D2 regulation.

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