Effect of propranolol on the metabolism of thyroid hormones

The effect of propranolol on thyroxine (T4) and 3,5',3'-triiodothyronine (T3) plasma concentrations, fractional disappearance rates (k), metabolic clearance rates (MCR) and catabolic rates has been investigated in young pigs. The animals were examined in the period 18-24 h after feeding. Plasma concentrations of T3 were lower after treatment with propranolol, but T4 was not significantly affected. The k value of T4 was decreased by propranolol but that for T3 was unaffected. The MCR of T4 and the catabolic rates of both hormones were reduced by propranolol. The reduction in metabolic rate after propranolol is thus probably related to its action on thyroid hormone metabolism.     

Role of thyroid hormones in regulation of sphingomyelin metabolism in the liver.

Inhibition of thyroid gland function in rats with mercasolil sharply decreased thyroxine and triiodothyronine levels in blood serum and increased acid sphingomyelinase activity and sphingomyelin content in liver. Thyroxine injected into hypothyroid rats normalized the sphingomyelin content, reduced the free ceramide content, and further increased the acid sphingomyelinase activity in liver. Thyroxine stimulated de novo sphingomyelin synthesis. Changing the thyroid status of the rats did not influence the free sphingosine content. Thyroxine blocks the accumulation of free sphingosine in the liver during activation of sphingomyelinases.     

Regulation of prostaglandin metabolism: inhibition of 15-hydroxyprostaglandin dehydrogenase by thyroid hormones

15-Hydroxyprostaglandin dehydrogenase has been purified from swine kidney to a specific activity of near 100 miliunits per mg of protein. The purified enzyme was found to be inhibited by thyroid hormone analogues of which triiodothyroacetic acid was the most potent inhibitor. The concentration required for 50% inhibition was 5 μM for triiodothyroacetic acid. The inhibition by thyroid hormones was uncompetitive and non-competitive with regard to NAD⁺ and prostaglandin E₁, respectively. The sensitivity of this enzyme to thyroid hormones suggests that these hormones may regulate the metabolism of prostaglandins $\text{in vivo}$.     

Metabolism of the thyroid hormones

This review covers the current knowledge about the various metabolic pathways involved in the conversion of thyroid hormones to the thyromimetically active and inactive iodothyronines. The concerted mechanism of systemic and local production of iodothyronines by tissue-specific iodothyronine deiodinase isozymes will ultimately determine the expression of thyroid hormone action. This is exemplified for the regulation of synthesis and release of TSH by iodothyronines at the pituitary level. Iodothyronine metabolites, e.g. Triac, rT3 and T3 amine may modulate TSH secretion, and alterations of local pituitary deiodination (e.g. iopanoate inhibition) influence diurnal TSH secretion without changing TRH-dependent episodic TSH secretion pattern. A summary of structure-activity relationships of greater than 200 naturally occurring and synthetic ligands of rat liver type I iodothyronine deiodinase isozyme propylthiouracil-sensitive) in vitro allows the design of iodothyronine analogues which either serve as specific substrates or antagonists of iodothyronine binding and metabolizing proteins. Furthermore, a complete picture of the ligand-complementary active site of the type I isozyme can be derived. A synthetic 'structurally optimized' iodothyronine-analogue flavonoid inhibitor of the type I deiodinase is able to displace T4 from binding to thyroxine-binding prealbumin and leads to unexpected organ-specific alterations of thyroid hormone metabolism and expression of thyroid hormone actions in an animal model. Therefore, for a complete understanding of thyroid hormone metabolism and action, thyroid hormone transport, cellular compartmentalization, and alternate pathways also have to be considered.     

Regulation of enzymes of glucose metabolism and lipogenesis in diabetic rat liver by thyroid hormones

Experimental diabetes in rats is associated with a degree of hypothyroidism. Hepatic enzymes involved in carbohydrate and lipid metabolism were estimated in control (untreated), control +T3 treated, alloxan diabetic and alloxan diabetic + T3-treated rats. The key glycolytic enzymes, phosphofructokinase and pyruvate kinase, were decreased in activity in diabetes and unchanged by further treatment with T3. In contrast, certain enzymes involve in lipogenesis, ATP-citrate lyase 'malic' enzyme and 6-phosphogluconate dehydrogenase, which were decreased in activity in diabetes, were increased to, or above, control values when diabetic rats were treated with T3. It is suggested that T3 deficiency may play a role in the decrease in enzyme activities observed in experimental diabetes, in particular, some enzymes associated with lipogenesis and the provision of NADPH.