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Biomedical subjects

M A Brenner

Publications and source records attributed to M A Brenner.

31 records · Page 2Linked to original sources
PubMed1978

Mitochondrial thyroid hormone receptor: localization and physiological significance.

Binding studies of thyroid hormone to submitochondrial fractions from rat liver suggest that the component responsible for high-affinity, low-capacity (saturable) binding of hormones arises from the inner mitochondrial membrane. The partially purified component, approximately 150,000 daltons, appears to be half protein and half lipid, largely phospholipids, tentatively identified as lecithin, phosphatidyl ethanolamine, and cardiolipin. A similar hormone-binding macromolecule was found in mitochondria from rabbit kidney, from human liver and kidney, and from rat kidney, myocardium, skeletal muscle, intestinal mucosa, whole small intestine, adipose tissue, and lung. It was absent from mitochondria of adult rat brain, spleen, and testis, organs calorigenically unresponsive to thyroid hormones injected in vivo, but was present in mitochondria from brains of rats 12 days old and younger. The organ distribution of the hormone-binding protein and its presence in neonatal brain mitochondria supports the biological relevance of the mitochondrial component as a thyroid hormone receptor.

Animals↗
PubMed1977

Thyroid hormone action: the mitochondrial pathway.

The subcellular compartments have been investigated to compare proteins capable of binding triiodothyronine and thyroxine; specific binders have been found in cytosol, nuclei, and mitochondria from rat liver and kidney. The binding protein from the inner mitochondrial membrane had the highest association constant (greater than 10(11) liters per mole), suggesting possible direct hormone action on the mitochondria. Binding of hormone analogs was found to be related to known physiological potency, and stereospecific discrimination between L- and D-thyroxine was observed. The saturable receptor was found in the mitochondrial membranes of rat liver, kidney, myocardium, and skeletal muscle but not in mitochondria from the unresponsive tissues: brain, spleen, and testis. Oxidative phosphorylation by mitochondrial vesicles from hypothyroid rats increased after the addition of physiological concentrations of triiodothyronine, which corroborated direct hormone action on mitochondria.

Animals↗
PubMed1973

Conversion of thyroxine to triiodothyronine by cultured human cells.

Human liver and kidney cells convert 6 to 10 percent of added thyroxine to triiodothyronine in vitro at 37 degrees C. This extent of conversion is ten times greater than that in control studies with killed cells. Conversion is evident within 10 minutes and appears to be maximal within 1 hour. Greater net triiodothyronine formation results if greater amounts of exogenous thyroxine are added to the system, with no plateau evident even at very high thyroxine concentrations. The addition of high concentrations of nonradioactive triiodothyronine resulted in no evident inhibition of the conversion.

Biotransformation↗
PubMed1971

Preparation and properties of thyroxine-binding alpha globulin (TBG).

Thyroxine-binding alpha globulin (TBG) in human serum was isolated from Cohn fractions IV-5,6 and IV-4 by (1) chromatography on carboxymethyl (CM) cellulose, (2) gel filtration on Sephadex G-200, (3) chromatography on diethylaminoethyl-Sephadex, (4) a novel procedure of "double-gel" electrophoresis, and (5) preparative polyacrylamide gel electrophoresis. The protein was homogeneous by analytical disc gel electrophoresis, immunoelectrophoresis, and ultracentrifugal analyses (sedimentation velocity and sedimentation equilibrium), and after addition of thyroxine-(125)I showed a constant specific radioactivity on polyacrylamide electrophoresis. The sedimentation and diffusion coefficients were s(20, w), 3.0 x 10(-13) sec, and D(20, w), 8.05 x 10(-7) cm(2).sec(-1), and the molecular weight obtained by sedimentation equilibrium was 36,500. Gel filtration studies on Sephadex G-200 demonstrated that the protein had the same elution volume as that of native TBG in serum, apparently excluding the possibility of a subunit of the native protein. Chemical composition was ascertained by amino acid and carbohydrate analyses. The maximal thyroxine (T4)-binding capacity measured by reverse flow paper electrophoresis was 15,000 mug per g of protein, representing more than 2100 times that of the starting material, or about 5000 times that of whole serum. Based on the molecular weight obtained, the TBG preparation could bind 0.7 mole T4 per mole of protein, suggesting a single binding site. The association constant for T4 was estimated to be of the order of 10(10) by competitive binding studies employing TBG and T4-binding prealbumin (TBPA).

Alpha-Globulins↗
PubMed1970

Conversion of thyroxine to triiodothyronine in normal human subjects.

The conversion of thyroxine to triiodothyronine, previously demonstrated in athyreotic human subjects, has been investigated in normal subjects who were given intravenous injections of purified thyroxine labeled with carbon-14 in ring A and in the alanine side chain. Evidence for the conversion of T4 to T3 was provided by the finding of carbon-14 in the T3 fraction isolated from serums. It is estimated that an appreciable fraction of T4 may be transformed to T3 in normal man.

Carbon Isotopes↗
PubMed1969

Determination of triiodothyronine concentration in human serum.

A simplified method has been described for the measurement of triiodothyronine (T3) in human serum. The sensitivity was sufficient for determinations on hypothyroid as well as normal and thyrotoxic sera. The values obtained have been in reasonable agreement with a double isotope derivative assay. The normal T3 concentration in human serum approximates 0.2 mug/100 ml; the mean +/-SD of 31 normal sera was 220 +/-27 ng/100 ml. Elevations were observed in sera from 40 patients with thyrotoxicosis (752 +/-282 ng/100 ml), and diminutions were found in sera from 10 hypothyroid patients (98+/-48 ng/100 ml). In rare instances thyrotoxicosis may be due to elevated serum T3 with normal thyroxine (T4) concentration. The incidence of this condition remains to be determined. In approximately half the cases with low serum T4 after (131)I therapy, the eumetabolic state may be maintained by normal or elevated T3 concentration. From these data and kinetic studies indicating a rapid turnover it may be inferred that T3 rather than T4 may be the more important hormone in health and in disease.

Chromatography, Ion Exchange↗