The concurrent induction of hepatic α-glycerophosphate dehydrogenase and malate dehydrogenase by thyroid hormone

Tarentino, Anthony L.; Richert, Dan A.; Westerfeld, W. W.

doi:10.1016/0304-4165(66)90193-0

Cited by 70 publications

(22 citation statements)

References 20 publications

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“…One possibility is that the sites for initiation of induction of these hepatic enzymes are not the nuclear sites which are being quantitated. Although this possibility cannot be rigorously excluded it seems highly unlikely on the basis of the corollary data reviewed in the Introduction, especially those studies which specifically indicate that ME and a-GPD induction is inhibited by agents such as actinomycin D and a-amanitine known to block transcription (27)(28)(29)(30)(31). Further, hepatic a-GPD and ME are excellent indices of thyroid hormone action at the cellular level (32,33) and a strong correlation between the activity of thyroid hormone analogues and nuclear binding has been established (34).…”

Section: Discussionmentioning

confidence: 99%

Nonlinear (amplified) relationship between nuclear occupancy by triiodothyronine and the appearance rate of hepatic alpha-glycerophosphate dehydrogenase and malic enzyme in the rat.

Oppenheimer¹,

Schwartz²,

Gutfeld³

1978

J. Clin. Invest.

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A B S T R A C T Three separate approaches were applied to examine the general relationship between R, the rate of induction of specific enzymes (mitochondrial a-glycerophosphate dehydrogenase and cytosolic malic enzyme) and q, the fractional nuclear occupancy by triiodothyronine in male Sprague-Dawley rats. Daily 200-,ug injections of triiodothyronine per 100 g body wt for 7 days resulted in saturation of the hepatic nuclear sites and the achievement of an apparent new steady state of enzyme levels. The increase achieved over base-line hypothyroid levels was then compared with the increment over hypothyroid base line characteristic of intact euthyroid animals with 47% of nuclear sites occupied. The maximal theoretical rate of steadystate enzyme induction could be projected on the basis of the observed maximal increase in enzyme activity observed 1 day after the injection of graded doses of hormone and X, the known fractional rate of enzyme dissipation. The 24-h dose-response studies were used to generate R as a continuous function of q, both in hypothyroid as well as in euthyroid animals. This approach involved the numerical solution of an ordinary differential equation describing the rate of change of enzyme as a function of R, which was assumed to be uniquely related to q. Results of these analyses indicated that the ratio of the maximal rate of induction

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Section: Discussionmentioning

confidence: 99%

Nonlinear (amplified) relationship between nuclear occupancy by triiodothyronine and the appearance rate of hepatic alpha-glycerophosphate dehydrogenase and malic enzyme in the rat.

Oppenheimer¹,

Schwartz²,

Gutfeld³

1978

J. Clin. Invest.

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“…Inhibitors of protein synthesis both at the transcriptional and translational levels block the enzyme response (6,8,9,13). The increase in enzyme activity appears to be a reflection of increased mass as demonstrated by the use of specific antisera to ME and measurement of increased rate of leuicine incorporation into this enzyme (16,18,20,22).…”

Section: Abstract Experimentsmentioning

confidence: 99%

“…Since the studies described above were carried out only in FIGURE 6 Relationship between increments in a-GPD (Upper panel) and ME (Lower panel) and terminal plasma T3 concentrations in paired experiments carried out for 24 and 36 h. Graded i.v. pulse doses of T3 were injected at t = 0.…”

Section: Figure 1 Response Of Mitochondrial A-gpd (Upper Panel)mentioning

confidence: 99%

Stimulation of hepatic mitochondrial alpha-glycerophosphate dehydrogenase and malic enzyme by L-triiodothyronine. Characteristics of the response with specific nuclear thyroid hormone binding sites fully saturated.

Oppenheimer¹,

Silva²,

Schwartz³

et al. 1977

J. Clin. Invest.

153

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A B S T R A C T Experimentswere designed to analyze the relationship of a single i.v. dose of triiodothyronine (T3), the level of plasma and hepatic nuclear T3 attained, and the tissue response as reflected in increased activity of hepatic mitochondrial a-glycerophosphate dehydrogenase (a-GPD) and cytosol "malic enzyme" (ME). These studies were carried out in euthyroid rats by varying the dose of T3 injected and the time at which the animals were killed and the enzyme levels measured. The plasma T3 concentration was determined and the fraction of nuclear sites occupied at any time t was calculated from the known plasma:nuclear relationship. As a first step, the analysis was confined to the limiting situation in which all nuclear sites were effectively saturated. The following additional information was required and obtained: A proportional relationship between the half-neutralizing volume of a specific antiserum to malic enzyme and the activity of malic enzyme was established, thus confirming previous reports that the increase in enzyme activity induced by T3 is due to increased enzyme mass. The absolute refractory period immediately after i.v. injection of T3, during which no enzyme response could be detected, was determined. This was shown to be 13.4 h for a-GPD and 8.2 h for ME.Lastly, the tI of the enzyme decay after pulse injection of T3 was measured. This was similar for both (SD) days for ME.The results of these studies indicated that the extent of hepatic response appears limited by full occupancy of a set of intracellular receptor sites by T3 which is in rapid equilibrium with the plasma hormone pool. The kinetic properties of the receptors, as functionally defined in these studies, resemble those associated with the recently described specific nuclear T3 sites. These data per se are thus compatible with but do not prove a nuclear site of initiation of hormone effect. They do allow the development of an internally consistent mathematical model which permits prediction of enzyme response when the receptor sites are fully occupied for a given length of time after the i.v. injection of hormone.A separate series of studies was carried out in thyroidectomized rats. The response characteristics of a-GPD were similar to those observed in euthyroid animals. In contrast, however, the early response of ME to pulse injections of T3 was very much reduced in hypothyroid animals as compared to euthyroid animals in which nuclear sites were saturated for comparable periods. These findings raise the possibility that a factor required for the induction of malic enzyme but not a-GPD is deficient in the hypothyroid state.

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“…It is the activity of the mitochondrial enzyme which is reduced in subcutaneous adipose tissue of obese subjects (1). This same enzyme increases in activity with thyroid treatment in some species (4,5), though not in all (13). The experiments reported in Table III (medium D) show that pretreatment with triiodothyronine increased the activity of this enzyme in human fat.…”

Section: Discussionmentioning

confidence: 87%

“…Depressed oxidation of this substrate by mitochondria might be expected to enhance the development of obesity by increasing the supply of sn-glycerol-3-phosphate for synthesis of triglyceride. The metabolism of sn-glycerol-3-phosphate can be increased in experimental animals by treatment with thyroid hormones (4,5) and manipulation of dietary intake (6). The present studies were designed to determine whether similar manipulations could alter the metabolism of sn-glycerol-3-phosphate in adipose tissue from obese patients.…”

Section: Introductionmentioning

confidence: 99%

Effect of diet and triiodothyronine on the activity of sn-glycerol-3-phosphate dehydrogenase and on the metabolism of glucose and pyruvate by adipose tissue of obese patients

Bray¹,

Mothon²,

Cohen³

1969

J. Clin. Invest.

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The concurrent induction of hepatic α-glycerophosphate dehydrogenase and malate dehydrogenase by thyroid hormone

Cited by 70 publications

References 20 publications

Nonlinear (amplified) relationship between nuclear occupancy by triiodothyronine and the appearance rate of hepatic alpha-glycerophosphate dehydrogenase and malic enzyme in the rat.

Nonlinear (amplified) relationship between nuclear occupancy by triiodothyronine and the appearance rate of hepatic alpha-glycerophosphate dehydrogenase and malic enzyme in the rat.

Stimulation of hepatic mitochondrial alpha-glycerophosphate dehydrogenase and malic enzyme by L-triiodothyronine. Characteristics of the response with specific nuclear thyroid hormone binding sites fully saturated.

Effect of diet and triiodothyronine on the activity of sn-glycerol-3-phosphate dehydrogenase and on the metabolism of glucose and pyruvate by adipose tissue of obese patients

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