Physiological disposition of <scp>d</scp>- and <scp>l</scp>-thyroxine in the rat

Tapley, Donald F.; Davidoff, Frank; Hatfield, W. B.; Ross, J. E.

doi:10.1152/ajplegacy.1959.197.5.1021

Cited by 46 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This difference may result from a greater depletion of liver glycogen stores (Table 1) and consequently more limited capacity for provision of glucose for the circulation. This would be compatible with the fact, that D-thyroxine is concentrated to a greater extent in the liver than L-thyroxine (Tapley et al 1959). The results support the view that the diffe¬ rences between L-thyroxine and D-thyroxine are only quantitative.…”

Section: Resultssupporting

confidence: 67%

Inhibition of insulin secretion by l-thyroxine and d-thyroxine treatment in rats under the influence of drugs affecting the adrenergic nervous system

Lenzen

Kücking

1982

Acta Endocrinologica

View full text Add to dashboard Cite

Both l-thyroxine and d-thyroxine induced an inhibition of glucose-induced insulin secretion with comparable time-and dose-dependent characteristics. l-thyroxine was ten times more potent than d-thyroxine. While l-thyroxine and a ten times higher dose of d\ x=r eq-\ thyroxine had a similar potency in inducing hyperthermia and hypocholesterolaemia, hyperglycaemia in response to d-thyroxine was less pronounced than in response to l-thyroxine. This difference may be explained by a greater depletion of liver glycogen stores and consequently more limited capacity for provision of glucose for the circulation. The results support the view that the differences between l-thyroxine and d-thyroxine are quantitative. Adrenergic contribution to l-thyroxineand d-thyroxine-induced inhibition of insulin secretion by rat pancreas is apparently of minor importance. Treatment of the rats with propranolol as well as with reserpine or 6-hydroxydopamine did not alleviate l \ x=r eq-\ thyroxine-or d-thyroxine-induced inhibition of insulin secretion by rat pancreas. Thyroid hormones decrease glucose tolerance and may induce diabetes in animals and in man prone to the diabetogenic action of thyroid hormones (Houssay 1948). L-Thyroxine as well as L-triiodothyronine are known to inhibit insulin secretion by the pancreas in rats and mice (Lenzen 1978; Len¬ zen & Klöppel 1978).p-Thyroxine has a biological activity much lower than that of the l.-isomer. The ratios between biological activity of D-thyroxine and L-thyroxine, however, vary greatly (Starr 1978). It has been claimed that D-thyroxine in contrast to l.-thyroxine is able to lower plasma cholesterol levels without concomitant increased blood glucose concentra¬ tions (Starr 1978).In the present investigation, time-and dosedependent effects of l.-thyroxine and D-thyroxine on glucose-induced insulin secretion by perfused rat pancreas were compared. We have used a specially pure preparation of D-thyroxine (Neudecker & Scheiffele 1971) to exclude the possibility of contamination with L-thyroxine.Hyperthyroidism increases sensitivity for catecholamines and many metabolic effects of thyroid hormones can be reproduced by application of catecholamines (Himms-Hagen 1967). In the pre¬ sent experiments, the contribution of the adrener¬ gic nervous system to the effects of i.-thyroxine and D-thyroxine on insulin secretion was studied by application of drugs which affect the adrenergic nervous system. Materials and MethodsChemicals i.-Thyroxine (sodium salt) and D-thyroxine (sodium salt, containing only 0.05% L-thyroxine and 0.5% D-triiodothyronine) (Neudecker & Scheiffele 1971) were kindly provided by Henning

show abstract

Section: Resultssupporting

confidence: 67%

Inhibition of insulin secretion by l-thyroxine and d-thyroxine treatment in rats under the influence of drugs affecting the adrenergic nervous system

Lenzen

Kücking

1982

Acta Endocrinologica

View full text Add to dashboard Cite

show abstract

“…Other studies, in which the two isomers of thyroxine were not administered simultaneously into the same experimental subject, found that the metabolic disposal of D-thyroxine was much faster than its L-isomer (16,17). The early work of Sterling, Lashof, and Man (18) had shown that after a single injection of L-[3',5'-'"'IiT4, the biological half-life of serum radioactivity in euthyroid subjects varied with a range of 5-10 days.…”

Section: Discussionmentioning

confidence: 99%

The integrity of the ether linkage during thyroxine metabolism in man

Pittman¹,

Read²,

Chambers³

et al. 1970

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T The structures of thyroxine metabolites after total deiodination bear on the mode of thyroxine (Ti) action in vivo. The present study was undertaken to determine the integrity of the ether linkage during thyroxine metabolism in man. Normal volunteers were given simultaneous intravenous injections of two thyroxines labeled with either "C or 'H on the opposite sides of the ether linkage, D,L-[a,f-'H]Ti and D,L-[phenolic ring-"C] T4. The ratio of alanine side chain to phenolic ring which was measured as 'H: "C ratio was found to remain constant in the serum, urine, and feces during the subsequent 3 wk. The disappearance rates of the 'H and 14C radioactivity from blood were similar. The values of half-life were in the range of 4.2-6.7 days. 51-63% of the 'H and 50-57% of the "C doses were recovered from urine and 13-20% of the 'H and 15-20% of the 14C doses were recovered from feces. Chromatography of the urinary metabolites confirmed that the phenolic ring and the nonphenolic ring including at least part of the side chain remained linked together. INTRODUCTIONWhen thyroxine interacts with the cellular constituents, certain degradative reactions other than deiodination may happen to the molecule. Conceivably these reactions may result in quinone formation of the phenolic ring and cleavage of the ether linkage. However, there are very few published reports on the metabolism of the carbon structure of thyroxine, and the data obtained from studies of the lower animals are controversial.

show abstract

“…For example, it has been shown that when administered parenterally, D-thyroxine is metabolized more rapidly and distributed differently than the L-isomer (19,20). In addition, the discrepancy between the potencies of these agents as measured in vivo and in vitro is not limited to the adenyl cyclase system (21)(22)(23)(24)(25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

Myocardial adenyl cyclase: activation by thyroid hormones and evidence for two adenyl cyclase systems

Levey¹,

Epstein²

1969

J. Clin. Invest.

161

View full text Add to dashboard Cite

ABS TR A CT The mechanism responsible for the hyperdynamic circulatory state in hyperthyroidism has not been defined. Although certain cardiac manifestations resemble those caused by excessive adrenergic stimulation, recent evidence suggests that thyroid hormone exerts an effect on the heart that is independent of the adrenergic system. Since the inotropic and chronotropic effects of norepinephrine appear to be mediated by activation of adenyl cyclase, the possibility that thyroxine and triiodothyronine are also capable of activating adenyl cyclase was examined in the particulate fraction of cat heart homogenates.L-thyroxine and L-triiodothyronine increased the conversion of adenosine triphosphate-'P (ATP-P)to cyclic 3',5'-adenosine monophosphate-P (3',5'-AMP-'P) by 60 and 45% respectively (P<0.01). A variety of compounds structurally related to the thyroid hormones, but devoid of thyromimetic activity did not activate adenyl cyclase: these included 3,5-diiodo-L-thyronine, L-thyronine, 3,5-diiodotyrosine, monoiodotyrosine, and tyrosine. D-thyroxine activated adenyl cyclase and half maximal activity was identical to that of the L-isomer. Although the beta adrenergic blocking agent propranolol abolished norepinephrine-induced activiation of adenyl cyclase, it failed to alter activation caused by thyroxine.When maximal concentrations of L-thyroxine (5 X 10O moles/liter) and norepinephrine (5 X 10' moles/liter) were incubated together, an additive effect on cyclic 3',5'-AMP production resulted. This investigation demonstrates: (a) thyroid hormone is capable of activating myocardial adenyl cyclase in vitro and (b) this effect is not mediated by the beta adrenergic receptor. Moreover, the additive effects of norepinephrine and thyroxine suggest that at least two separate adenyl cyclase systems are present in the heart, one responsive to norepinephrine, the other to thyroid hormone.

show abstract

Physiological disposition of d- and l-thyroxine in the rat

Cited by 46 publications

References 0 publications

Inhibition of insulin secretion by l-thyroxine and d-thyroxine treatment in rats under the influence of drugs affecting the adrenergic nervous system

Inhibition of insulin secretion by l-thyroxine and d-thyroxine treatment in rats under the influence of drugs affecting the adrenergic nervous system

The integrity of the ether linkage during thyroxine metabolism in man

Myocardial adenyl cyclase: activation by thyroid hormones and evidence for two adenyl cyclase systems

Contact Info

Product

Resources

About