Biomedical subjects

C A Kaiser

Publications and source records attributed to C A Kaiser.

38 records · Page 3Linked to original sources

PubMed1986

In vivo inhibition of the 5'-deiodinase type II in brain cortex and pituitary by reverse triiodothyronine.

To study the effect of rT3 on the 5'-deiodinase type II (5'D-II) of rat brain cortex and anterior pituitary, daily infusions of rT3 at rates of 0.5, 1.5, 4.5, and 13.5 nmol/day X 100 g body weight were given to a total of 87 hypothyroid rats. rT3 inhibited the 5'D-II activity in the total homogenate and in the microsomal fraction in the brain cortex, inhibition becoming significant (28-33%) with the infusion of 4.5 nmol/day X 100 g body weight, at serum levels of 2.4 pmol rT3/ml. Infusion of 13.5 nmol/day X 100 g body weight produced 71-73% inhibition. In homogenates of the anterior pituitary, inhibition was significant with infusions of 13.5 nmol/day X 100 g body weight (30%). To examine how rT3 might inhibit 5'D-II activity, labeled rT3 (137 muCi/day) was infused into 4 hypothyroid rats, and the rT3 content in the homogenate and in the cell subfractions was measured by HPLC. No rT3 was detectable in the nuclei, and less than 1% was found in the microsomal fraction. The infused rT3 was thus no longer present in the microsome preparations and homogenates. The inhibitory effect of rT3 was also compared with that of T4. Serum T4 levels of 45 pmol/ml were required in order to inhibit 5'D-II to the same extent as with 7 pmol rT3/ml. The requirement of this high serum level of T4 excludes the potential role of T4 impurities in the infused rT3 preparation. We therefore conclude that rT3 inhibits 5'D-II in brain cortex per se independently of T4.

Animals↗

PubMed1983

3'-isopropyl-3,5-diiodo-L-thyronine: a potent synthetic thyromimetic thyronine analog. Studies of its kinetics and biological potency in man and rats and its toxicology.

In order to compare phenolic and tyrosyl ring monodeiodination, we investigated 3'-isopropyl-3,5-diiodo-L-thyronine (DIIP), a potent thyronine analog which can only be monodeiodinated on the tyrosyl ring. A specific RIA was developed. The in vivo metabolism and biological potency of DIIP and T3 were compared. DIIP and T3 kinetic studies were performed in vivo using 40 male SIVZ rats who received 5 micrograms DIIP and 0.5 microCi 131I-T3. Blood samples were obtained for up to 15 h. The MCR of DIIP was 2.8 ml/h/100 g BW and the volume of distribution was 27 ml/100 g BW, corresponding values for T3 being 34 ml/h/100 g BW and 175 ml/100 g BW. Subacute toxicology studies in rats showed that DIIP was not more toxic than T3. On the basis of these results, experiments were performed in man. Five male subjects received 40 micrograms DIIP p.o. and blood samples were collected over 17 days. The MCR was 54 ml/kg . day, the volume of distribution 188 ml/kg and the fractional disappearance rate 0.0119/h. When given to an hypothyroid patient, 16-20 micrograms DIIP daily was sufficient to restore clinical and biochemical euthyroidism. These studies demonstrate that a decreased MCR can be accompanied by increased biological activity. It is suggested that the limited monodeiodination of DIIP is one of the factors explaining the differences observed in the potency and metabolism of DIIP and T3.

Adult↗