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.
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.
Alvarez
L
L
Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Burgueño
A
A
Zeni
S
S
Randi
A S
AS
Hernández
S
S
Hockl
P
P
Pisarev
M A
MA
Kleiman de Pisarev
D L
DL
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006042:Goiter / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013972:Thyrotropin / Q000097:blood; D014284:Triiodothyronine / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D014284:Triiodothyronine; C010642:3,3',5-triiodothyroacetic acid; D013972:Thyrotropin