scholarly journals Thyroxine action on the rat liver nuclear thyroid-hormone receptors. Binding of thyroxine to the nuclear non-histone protein and induction of mitochondrial alpha-glycerophosphate dehydrogenase activity

1983 ◽  
Vol 210 (2) ◽  
pp. 331-337 ◽  
Author(s):  
Y Yoshimasa ◽  
S Hamada
Keyword(s):  
Body Weight ◽  
Nuclear Receptor ◽  
Rat Liver ◽  
Dna Content ◽  
Binding Capacity ◽  
Simultaneous Administration ◽  
Histone Protein ◽  
Glycerophosphate Dehydrogenase ◽  
Serum T4 ◽  
T4 Conversion

The possibility that thyroxine (T4) itself exerts the hormonal effect in vivo on the rat liver nuclear receptor was studied with the aid of iopanoic acid (IOP), an inhibitor of the conversion of T4 into tri-iodothyronine (T3). After administration of 2.4 micrograms of T4/100 g body weight to hypothyroid rats for 7 days, T4 and T3 concentrations in serum and in the liver nuclear non-histone protein (NHP) were all increased to the hyperthyroid range. Hepatic mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) activity and DNA content increased significantly. The equilibrium association constant (Ka) of the nuclear T3 receptor was unchanged and the maximal binding capacity (Cmax.) increased 1.4-fold. Simultaneous administration of IOP (5 mg/100 g body weight) to the rats given 2.4 micrograms of T4/100 g body weight completely blocked the conversion into T3. The serum T4 was even more increased, whereas the serum T3 decreased to the hypothyroid range. Although the NHP-bound T4 was at a concentration comparable with the rats given T4 alone, no NHP-bound T3 was detected. Yet the alpha-GPD activity was elevated 2.8-fold and the DNA content increased to the same extent as observed in the rats given T4 alone. The Ka and Cmax. of the nuclear receptor were significantly decreased. After administration of 48 or 480 micrograms of T4/100 g body weight for 3 days, serum T4 and T3 were markedly increased. The NHP-bound T3 was also increased, but no NHP-bound T4 was detected. The alpha-GPD activity was markedly elevated, but the DNA content was unchanged. The Cmax. per g of liver was increased, whereas the Ka remained unchanged. Simultaneous administration of IOP to these animals could not completely block the T4 conversion. The observed hormonal effects in the absence of nuclear T3 indicate that T4 possesses the intrinsic hormonal activities on the rat liver. T4 is less potent in induction of alpha-GPD activity but as potent in increment of hepatic DNA as T3. Although the binding site for T4 is not fully characterized, it appears to be acidic NHP. T4 is an active hormone, yet is also a prohormone of T3, offering the closest analogy with testosterone.

Different alterations of nuclear triiodothyronine receptor capacity in liver and kidney induced by starvation and triiodothyronine administration

1985 ◽  
Vol 108 (2) ◽  
pp. 206-210 ◽  
Author(s):  
Hirotoshi Nakamura ◽  
Toshihiko Yokota ◽  
Hiroo Imura
Keyword(s):  
Body Weight ◽  
Nuclear Receptor ◽  
Rat Liver ◽  
Nuclear Protein ◽  
Binding Capacity ◽  
Association Constants ◽  
Liver And Kidney ◽  
Maximal Binding ◽  
Different Tissues

Abstract. Many studies have shown alterations in the number of nuclear triiodothyronine receptor (NT3R) under pathophysiologic situations. Most of these studies were performed on the rat liver and it is not known whether NT3R in different tissues exhibits an alteration similar to that in the liver. We compared the change of nuclear receptor capacity for T3 in the liver and kidney during starvation and after T3 injection. Fasting for 72 h decreased maximal binding capacity (Cmax) in the rat liver receptor to 67% of the control, while it did not significantly change Cmax in the kidney. These changes in Cmax were parallel to those of nuclear protein concentrations in both tissues. Daily sc injection of T3 (20 μg/100 g body weight) for 3 days also caused the different alteration of Cmax in the liver and kidney. After T3, hepatic NT3R increased to 182% of the control, but renal NT3R increased only to 136%. Association constants were the same in all groups. These results show that changes of NT3R capacity under some conditions vary in different tissues.

scholarly journals Sequential changes in rat liver nuclear tri-iodothyronine receptors and mitochondrial α-glycerophosphate dehydrogenase activity after administeration of tri-iodothyronine

1979 ◽  
Vol 182 (2) ◽  
pp. 377-382 ◽  
Author(s):  
Hirotoshi Nakamura ◽  
Satoshi Hamada ◽  
Hiroo Imura
Keyword(s):  
Dehydrogenase Activity ◽  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Rat Liver ◽  
Time Course ◽  
Delayed Response ◽  
Histone Proteins ◽  
Glycerophosphate Dehydrogenase ◽  
Receptor Concentration ◽  
Hormonal Modulation

The dynamics of the induction of nuclear tri-iodothyronine receptors and mitochondrial α-glycerophosphate dehydrogenase were studied in rat liver after a single injection of tri-iodothyronine. The maximal binding capacity (Cmax.) and association constant (Ka) of the nuclear receptors were determined by Scatchard analyses with and without correction for the endogenous tri-iodothyronine measured by radioimmunoassay. The administration of tri-iodothyronine induced sequential increases in the concentration of nuclear receptors and α-glycerophosphate dehydrogenase activity in the liver. The nuclear-receptor concentration was increased to 2.5 times that in the hypothyroid rat 1 day after the administration of hormone, and then decreased, with a half-life of about 2 days. α-Glycerophosphate dehydrogenase activity changed in parallel with the nuclear-receptor concentration, showing a delayed response. The total amount of non-histone protein in the liver was significantly increased 3 days after the administration. It seems likely therefore that the tri-iodothyronine-induced increase in nuclear-receptor concentration is responsible, at least in part, for the induction of this enzyme. The possibility is also suggested that nuclear receptors may be one of the non-histone proteins selectively synthesized at an early stage of the hormonal stimulation. Throughout the time course, the Ka values of the nuclear receptors for tri-iodothyronine remained unchanged, when corrected for endogenous tri-iodothyronine bound to the non-histone proteins, although they were apparently changed when the correction was not made. The results obtained provide further evidence for hormonal modulation of the nuclear receptors which is closely linked with the hormonal effect.

Study of the role of histidyl, tyrosyl, α- or ε-amino residues in the specific binding of 3,5,3'-triiodothyronine to rat liver nuclear receptors

1988 ◽  
Vol 117 (2) ◽  
pp. 159-165 ◽  
Author(s):  
Julius Brtko ◽  
Ján Knopp
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Rat Liver ◽  
Binding Capacity ◽  
Specific Binding ◽  
Biologically Active ◽  
Amino Groups ◽  
Trinitrobenzenesulfonic Acid ◽  
Receptor Molecule

Abstract. The role of histidyl, tyrosyl, α-or ε-amino residues of rat liver nuclear receptors for the specific binding of T3 was studied by chemically modifying the receptor molecule. The kinetics of the formation of N-carbethoxyhistidyl derivative from histidyl groups of nuclear receptors by diethylpyrocarbonate was examined. The modified nuclear receptor fraction was separated from diethylpyrocarbonate by gel filtration and the T3 binding parameters (Ka and MBC) at pH 8.0 were tested by Scatchard plot analysis. At 0.1 mmol/l diethylpyrocarbonate, the value of Ka was significantly (P < 0.01) decreased without any change in maximal binding capacity (MBC). The modification of α- or ε-amino groups of nuclear receptors by excess of trinitrobenzenesulfonic acid, 6.3 mmol/l at pH 8.5, resulted in a 4-fold increase in MBC of T3 specific binding without any change in Ka. In addition, acetylation of tyrosyl residues of nuclear receptors at pH 7.5 with an excess of 24 mmol/l N-acetylimidazole was performed. No changes in nuclear receptor Ka or MBC were observed after N-acetylimidazole treatment. Histidine and/or amino groups of the receptor molecule seem to hold a key position in the generation of the biologically active T3-nuclear receptor complex in the rat liver.

scholarly journals Tri-iodothyronine-induced increase in rat liver nuclear thyroid-hormone receptors associated with increased mitochondrial α-glycerophosphate dehydrogenase activity

1979 ◽  
Vol 182 (2) ◽  
pp. 371-375 ◽  
Author(s):  
S Hamada ◽  
H Nakamura ◽  
M Nanno ◽  
H Imura
Keyword(s):  
Thyroid Hormone ◽  
Dehydrogenase Activity ◽  
Nuclear Receptors ◽  
Rat Liver ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptor ◽  
Histone Protein ◽  
Glycerophosphate Dehydrogenase ◽  
Hormonal Modulation

The effect of tri-iodothyronine injection on the nuclear tri-iodothyronine receptor (putative thyroid-hormone receptor) was examined in rat liver. Nuclear receptors were extracted from isolated nuclei with 0.4 M-KCl, and their association constants (Ka) and maximal binding capacities (Cmax.) were determined by Scatchard analyses with and without correction for the endogenous hormone. The amount of endogenous tri-iodothyronine bound to non-histone protein was estimated on the basis of the specific radio-activity of [125I]tri-iodothyronine injected 2 h before the rats were killed. It was demonstrated that Cmax. of the nuclear receptors was 2.5-fold higher in severely hyperthyroid than in hypothyroid rats. However, irrespective of the thyroid status, the Ka of the receptors remained unchanged when corrected for endogenous tri-iodothyronine bound to non-histone protein. The validity of the correction was supported by experiments in vitro in which nuclear receptors were preincubated with unlabelled tri-iodothyronine. The increase in Cmax. of nuclear receptors was directly related to mitochondrial alpha-glycerophosphate dehydrogenase activity. These results suggest a hormonal modulation of the nuclear receptors which is associated with hormonal action.

Effects of 5-5'-Diphenyl-2-thiohydantoin (DPTH) and Thyroxine on the Ultrastructure and Chemical Composition of Rat Liver

1971 ◽  
Vol 29 ◽  
pp. 570-571
Author(s):  
E. A. Elfont ◽  
R. B. Tobin ◽  
D. G. Colton ◽  
M. A. Mehlman
Keyword(s):  
Chemical Composition ◽  
Rat Liver ◽  
Future Study ◽  
Mode Of Action ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Effective Inhibitor ◽  
Biochemical Effects ◽  
Glycerophosphate Dehydrogenase ◽  
Stimulation Of

Summary5,-5'-diphenyl-2-thiohydantoin (DPTH) is an effective inhibitor of thyroxine (T4) stimulation of α-glycerophosphate dehydrogenase in rat liver mitochondria. Because this finding indicated a possible tool for future study of the mode of action of thyroxine, the ultrastructural and biochemical effects of DPTH and/or thyroxine on rat liver mere investigated.Rats were fed either standard or DPTH (0.06%) diet for 30 days before T4 (250 ug/kg/day) was injected. Injection of T4 occurred daily for 10 days prior to sacrifice. After removal of the liver and kidneys, part of the tissue was frozen at -50°C for later biocheailcal analyses, while the rest was prefixed in buffered 3.5X glutaraldehyde (390 mOs) and post-fixed in buffered 1Z OsO4 (376 mOs). Tissues were embedded in Araldlte 502 and the sections examined in a Zeiss EM 9S.Hepatocytes from hyperthyroid rats (Fig. 2) demonstrated enlarged and more numerous mitochondria than those of controls (Fig. 1). Glycogen was almost totally absent from the cytoplasm of the T4-treated rats.

REGULATION OF THE ACTIVITIES OF THE ENZYMES INVOLVED IN THE METABOLISM OF STEROID HORMONES IN RAT LIVER: THE EFFECT OF 19-NORTESTOSTERONE AND THE INFLUENCE OF CYPROTERONE ACETATE ON THE ACTION OF TESTOSTERONE AND 5α-DIHYDROTESTOSTERONE

1974 ◽  
Vol 77 (2) ◽  
pp. 287-297 ◽  
Author(s):  
Rüdiger Ghraf ◽  
Edmund Rodney Lax ◽  
Hanns-Georg Hoff ◽  
Herbert Schriefers
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Rat Liver ◽  
Enzyme Activities ◽  
Cyproterone Acetate ◽  
Hydroxysteroid Dehydrogenase ◽  
Seminal Vesicles ◽  
Normal Male ◽  
Steroid Hydroxylases ◽  
Drug Leads

ABSTRACT The androgens testosterone and 5α-dihydrotestosterone, the anabolic drug 19-nortestosterone and the anti-androgen cyproterone acetate were investigated with regard to their modifying action on the sexual differentiation of the activities of rat liver enzymes involved in steroid hormone metabolism. The activities of the enzymes (Δ4-5α-hydrogenase, 20-ketoreductase, 3α-and 3β-hydroxysteroid dehydrogenase, NAD- and NADP-dependent Δ4-3β-hydroxysteroid dehydrogenase, total steroid hydroxylases, 7α- and 16α-hydroxylase) were determined in cell-free liver fractions of male animals castrated on day 25 of life and killed on day 90; and of castrated animals which, from day 75 to 89 received daily sc injections (0.3 mg/100 g body weight) of the anabolic drug or the androgen only or in combination with cyproterone acetate (3 mg/100 g body weight). With the exception of 7α-hydroxylase castration leads to a feminization of the enzyme activity pattern. However, the degree of feminization varies from enzyme to enzyme. The administration of testosterone or of 5α-dihydrotestosterone reverses the effect of castration. With 5α-dihydrotestosterone activity values were reached which in some cases were significantly higher than those obtained with testosterone. Although both androgens restored the enzyme activities to the normal male values, neither androgen was able to compensate for the weight loss of the seminal vesicles in the dose administered. The administration of 19-nortestosterone in the same dose as testosterone is only 30 % as effective in restoring the weight loss of the seminal vesicles, but leads to identical activities of Δ4-5α-hydrogenase and of hydroxysteroid dehydrogenases as are found for testosterone. 19-Nortestosterone is without influence on the activities of total steroid hydroxylases and of 16α-hydroxylase. 16α-Hydroxylase is the only enzyme in which the activity enhancing effects of testosterone or of 5α-dihydrotestosterone can be completely blocked by the simultaneous administration of the anti-androgen cyproterone acetate. In all other enzyme activities the anti-androgen does not interfere with the effect of the androgens although it blocks their action on the weight restitution of the seminal vesicles by 60–70 %. 7α-Hydroxylase does not exhibit any androgen dependency. Neither castration nor the subsequent administration of the two androgens, or of the anabolic drug leads to any alterations in activity. However, it is interesting to note that the administration of cyproterone acetate does cause an increase in activity.

Insulin and central regulation of spontaneous fattening and weight loss

1985 ◽  
Vol 249 (2) ◽  
pp. R203-R208
Author(s):  
R. B. Melnyk ◽  
J. M. Martin
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Weight Gain ◽  
Energy Balance ◽  
Binding Capacity ◽  
Insulin Receptors ◽  
Insulin Binding ◽  
Strong Positive Correlation ◽  
Central Regulation ◽  
Isolated Pancreatic Islets

Insulin binding to receptors in a partially purified hypothalamic membrane preparation is altered by prolonged starvation. To define further the relationship between hypothalamic insulin binding and energy balance, we studied the Richardson's ground squirrel, a hibernator that exhibits spontaneous 6- to 8-mo body weight cycles when kept in constant conditions. Isolated pancreatic islets from squirrels killed during the weight gain phase had greater glucose-stimulated insulin secretion than those from weight loss phase animals, and adipocytes showed significantly greater glucose incorporation into total lipid in response to insulin. Differences in lipogenesis were not attributable to changes in insulin-binding capacity. Hypothalamic tissue from weight gain phase animals bound more insulin than that from weight loss phase animals. Maximal binding was correlated with pancreatic islet responsiveness and maximal insulin-stimulated lipogenesis. The strong positive correlation between peripheral metabolic events associated with spontaneous alterations in energy balance and the binding kinetics of hypothalamic insulin receptors suggests that insulin may play an important role in the central regulation of body weight.

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