Comparison of the Effects of 3,5,3'-Triiodothyroacetic Acid and Triiodothyronine on Goiter Prevention and Involution and on Hepatic and Skeletal Parameters in Rats

Abstract

3,5,3'-triiodothyroacetic acid (TRIAC) has been used to suppress pituitary TSH secretion with reported attenuation of extrapituitary effects. We investigated whether equivalent doses of T (3) and TRIAC preventing the induction of goiter by methimazole (MMI) had a different or similar impact on peripheral tissues, such as liver and bone. In particular, we compared the effects of both compounds on the activity of the hepatic thyroid hormone-responsive enzymes, malic enzyme and L-glicerol-3-P dehydrogenase; bone mineral density and biochemical parameters of bone turnover, such as bone alkaline phosphatase (b-ALP) and the carboxy-terminal telopeptide region of type I collagen (beta-CTX); and the activity of thyroid ornithine decarboxylase (ODC). We also compared the effects of T (3) and TRIAC on the involution of MMI-induced goiter. Our results showed that TRIAC was more effective than T (3) to reduce MMI-induced goiter in a short-term goiter involution assay. TRIAC increased hepatic enzymes activity and beta-CTX levels, a parameter of bone resorption, more than T (3). However, bone mineral density was not altered by either treatment. Both compounds even reduced ODC activity at doses that were not effective at the pituitary level. These results demonstrate increased TRIAC hepatic and antigoitrogenic activity compared to T (3). TRIAC induces an imbalance in bone remodeling without affecting bone mineral density. Further studies are required to clarify this point.

Triiodothyroacetic acid in health and disease

“…In hypothyroid animals on the same TA 3 dose, an increase in β-CTX serum levels was observed without concomitant increase in serum bALP. However, BMD did not differ significantly between TA 3 -treated and control animals (Alvarez et al 2004).…”

“…In addition, the BMD of the femur did not differ significantly between TA 3 -treated and control animals (Alvarez et al 2004). In hypothyroid animals on the same TA 3 dose, an increase in β-CTX serum levels was observed without concomitant increase in serum bALP.…”

“…TA 3 also effectively induces the expression of T 3 -responsive genes in the liver, including Dio1, to a similar extent as T 3 (Juge-Aubry et al 1995, Liang et al 1997, Alvarez et al 2004, MedinaGomez et al 2008. No changes in serum cholesterol and lipid levels or biliary excretion were observed after treatment of euthyroid rats for 4 weeks with 200 µg TA 3 / kg/day (Van Zyl 1957, Autissier et al 1980.…”

“…However, daily injection of 250 µg/kg TA 3 in euthyroid rats for 40 days did not increase serum bone alkaline phosphatase (bALP) or carboxy-terminal telopeptide region of type I collagen (β-CTX), which are markers for bone formation and resorption, respectively (Alvarez et al 2004). In addition, the BMD of the femur did not differ significantly between TA 3 -treated and control animals (Alvarez et al 2004).…”