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PubMed1989

The significance of hepatic microsomal enzyme induction and altered thyroid function in rats: implications for thyroid gland neoplasia.

Hepatic microsomal enzymes play an important role in thyroid hormone homeostasis. Glucuronidation of thyroxine is the rate limiting step in the biliary excretion of thyroxine in the rat; the monodeiodinases are important in the conversion of T4 to T3 and reverse T3 and subsequent deiodinations. Phenobarbital is known to affect thyroid function in rats due to an alteration of hormone disposition. We have further characterized these effects and have demonstrated that phenobarbital increases the biliary excretion of thyroxine glucuronide primarily as a result of an induction of hepatic thyroxine glucuronyltransferase. Studies on the mode of action for phenobarbital promotion of thyroid follicular neoplasia were conducted using an initiation-promotion model established by Hiasa et al (35). In this model, we demonstrated that supplemental administration of thyroxine blocked the promoting effect of phenobarbital and furthermore, using various dosages of thyroxine, we observed that the tumor promoting effect of phenobarbital was directly proportional to the level of plasma TSH. The results of these studies support the hypothesis that the tumor promoting effect of phenobarbital in the thyroid gland is mediated via increased secretion of pituitary TSH as a compensatory response to the known effects of phenobarbital on peripheral thyroid hormone disposition. Since a number of microsomal enzyme inducing agents have increased the incidence of thyroid follicular neoplasia in rat carcinogenicity studies, thyroid function should be assessed and a secondary mechanism of hormone imbalance should be considered in the interpretation of the significance of these findings in rodents.

Animals↗
PubMed1962

Is memory a matter of enzyme induction?

Variations in cholinesterase and RNA concentrations and in levels of neural activity have been linked to learning. These three groups of experimental evidence suggest that the basis of memory lies in an increase of the concentrations of enzymes associated with transmitter substances, as a long-lasting effect of stimulation. Biological precedent exists in microbial physiology.

Acetylcholinesterase↗
PubMed1981

Plasminogen activator: analysis of enzyme induction by ultraviolet irradiation mapping.

Ultraviolet irradiation mapping techniques have previously been used to study the organization of eucaryotic gene classes and transcription units. We used the same method to probe some regulatory phenomena observed in the induction of plasminogen activator (PA) biosynthesis: PA synthesis in chicken embryo fibroblasts is induced by tumor-promoting phorbol esters and by retinoic acid; furthermore, PA induction by phorbol esters is synergistic with transformation, being 10- to 20-fold greater in virus-transformed cells than in normal cells. We found that the ultraviolet irradiation inactivation cross sections for PA induction by phorbol esters and by retinoate differed significantly, suggesting that these agents induce PA biosynthesis by different mechanisms. On the other hand, the ultraviolet irradiation sensitivity of phorbol ester induction in normal chicken embryo fibroblasts was the same as in transformed cells, indicating that the synergism of transformation and phorbol esters is probably not due to different pathways of PA induction.

Animals↗
PubMed1985

[Enzyme inductive effect of zixoryn (3-trifluoromethyl-alpha-ethyl-benzhydrol) in neonatal jaundice].

Zixoryn, (3-trifluoromethyl-alfa-aethyl-benzhydrole) is a new product of the Hungarian Chemical Works of Gedeon Richter Ltd. It induces the mixed function oxydase enzyme system of the endoplasmic reticulum of the liver and has no other pharmacological effects. We have studied the effect of Zixoryn on early hyperbilirubin-aemia. 42 neonates were studied, 21 of them were randomly assigned to be treated and the others served as control group Zixoryn treatment consisted of drops containing 10 mg Zixoryn per ml in a single 20 mg/kg body weight dose through a gastric tube. Results are summarized in Fig. 2. It shows the mean se bi levels during the first six days of life. It is remarkable that the decline of se bi level was much faster in the treated than in the control group. On the third day the difference between the two groups was significant. We may conclude that after Zixoryn administration the se bi level of otherwise healthy newborns decreased significantly faster than that of untreated neonates. No side-effects what so ever were observed. The administration is easy, a single oral dose has a satisfactory effect.

Benzhydryl Compounds↗