Differences between the effects of thyroxine and tetraiodothyroacetic acid on TSH suppression and cardiac hypertrophy.
OBJECTIVE
We earlier reported marked qualitative differences between the effect of 3,5,3'-tri-iodothyroacetic acid (Triac) and tri-iodothyronine (T3) on cardiac hypertrophy at equivalent thyroid-stimulating hormone (TSH)-suppressive doses. We have now extended these studies to specific cardiac parameters. Due to its rapid metabolic clearance rate, Triac is not suitable for TSH suppression and therefore the slowly metabolized 3,5,3',5'-tetraiodothyroacetic acid (Tetrac), the precursor of Triac, was studied.


METHODS
Hypothyroid rats were infused over 13 days with 1.5-40.5 nmol Tetrac/day per 100 g body weight (BW) or with 0.5-13.5 nmol thyroxine ((4)T4)/day per 100 g BW.


RESULTS
The responses of serum TSH and of hepatic monodeiodinase type 1 were parallel for both hormones, their potency ratios could therefore be compared. Tetrac was revealed as being only half as active on hepatic monoiodinase type 1 despite a similar serum TSH levels. Tetrac can therefore be considered to have a preferential action on serum TSH suppression. The cardiac effects on Ca2+-ATPase (SERCA 2a) and monodeiodinase type 1 activity were qualitatively different and therefore one cannot give an overall quantitative estimate of these differences. The results showed clearly, however, that Tetrac is less efficient for all parameters studied, namely induction of cardiac hypertrophy, alpha-myosin heavy chain mRNA, monodeiodinase type 1 activity and mRNA levels of the sarcoplasmic SERCA 2a.


CONCLUSIONS
We postulate therefore that, in the rat and possibly in man, Tetrac could represent a favorable alternative for suppression of serum TSH levels.
Lameloise
N
N
Thyroid Unit, Division of Endocrinology and Metabolism, Department of Medicine, University of Geneva, CH 1211 Geneva 4, Switzerland.
Siegrist-Kaiser
C
C
O'Connell
M
M
Burger
A
A
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000235:genetics; D006332:Cardiomegaly / Q000139:chemically induced* / Q000473:pathology; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013972:Thyrotropin / Q000037:antagonists & inhibitors* / Q000097:blood; D013974:Thyroxine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D007527:Isoenzymes; D012333:RNA, Messenger; D013972:Thyrotropin; D007453:Iodide Peroxidase; D000252:Calcium-Transporting ATPases; C011126:tetraiodothyroacetic acid; D013974:Thyroxine