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Biomedical subjects

K Sterling

Publications and source records attributed to K Sterling.

At least 37 records · Page 2Linked to original sources
PubMed1981

Acquired refractoriness to thyroid hormone action in treated toxic nodular goiter.

A case of apparent target organ refractoriness to thyroid hormones has been observed during the recovery phase of toxic nodular goiter after 131I therapy. The serum PBI was normal before the onset, but elevated serum PBI and T4 concentrations were observed during the toxic phase, and after recovery, with elevated T3 as well. The case differed in important respects from the congenital, hereditary disorder known as the Refetoff syndrome.

Aged↗
PubMed1980

Rapid effect of triiodothyronine on the mitochondrial pathway in rat liver in vivo.

Intravenous infections of minute doses of triiodothyronine were administered to thyroidectomized rats 30 minutes before they were killed. Hepatic mitochondria were isolated rapidly and formation of adenosine triphosphate and consumption of oxygen were assessed by a 2-minute incubation. Hormone injection enhanced formation of adenosine triphosphate 114 to 217 percent over control values, with a proportionate increase in consumption of oxygen. The ratio of phosphate to oxygen was about 2.0, signifying tightly coupled oxidative phosphorylation. Stimulation was not abolished by injection of cycloheximide, puromycin, actinomycin D, or chloramphenicol 1 hour before the rats were killed. This signifies direct mitochondrial stimulation by triiodothyronine in the absence of protein synthesis.

Adenosine Triphosphate↗
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↗
PubMed1978

Partial purification of thyroid hormone receptor from mitochondrial inner membrane: evidence for a physiologic role.

Recently we described a protein component, from the inner mitochondrial membrane, which binds thyroid hormone with high affinity, low capacity (saturable) characteristics. This partially purified rat liver mitochondrial membrane component appears to be a 150,000 daltons lipoprotein complex. Phospholipids, tentatively identified as lecithin, phosphatidyl ethanoamine, and cardiolipin, appear to constitute 50% of this complex. A similar hormone binding marcomolecule was also found in mitochondria from rabbit kidney, as well as human liver and kidney. In the rat this saturable thyroid hormone binding component was found in mitochondria from liver, kidney, myocardium, skeletal muscle, intestinal mucosa, whole small intestine, adipose tissue, and lung. It was absent from the mitochondria of adult brain, spleen and testis, organs known to be calorigenically unresponsive to thyroid hormones injected in vivo. In contrast, neonatal rat brains contain the protein with binding constants similar to those of neonatal or adult rat liver mitochondria, but in older rat brains (14 and 17 days) the saturable binding was no longer present, as in adult brain. These data provide strong support for 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↗
PubMed1975

Thyroid hormone binding by a component of mitochondrial membrane.

The thyroid hormone, triiodothyronine, has been shown to be bound by the intranuclear chromatin protein associated with active DNA, where it is believed to stimulate transcription. Evidence exists that the thyroid hormones have direct action not only on nuclei, but also on mitochondria. Threfore, specific proteins that bind thyroid hormones in the mitochondria should be demonstrable. Mitochondria were isolated from homogenized rat livers by sedimentation through 0.25 M sucrose solution, followed by washing four times to free them of microsomes. Strong binding of thyroid hormones was observed in mitochondrial fractions prepared from both the membranes and the matrix. After incubation in an ice bath with increasing amonts of triiodothyronine with added tracer [125I]triiodothyronine, the matrix infrequently contained specific saturable receptor sites, but usually exhibited strong "nonspecific" interaction...

Animals↗
PubMed1975

Serum triiodothyronine concentration in thyroid storm.

Serum triiodothyronine levels were elevated in 6 patients with thyroid storm (769 plus or minus 181 ng/100 ml) but the values observed were not significantly different from those found in uncomplicated thyrotoxicosis (752 plus or minus 282 ng/100 ml). This observation suggests that the pathogenesis of thyroid storm resides in mechanisms other than a simple increase in serum triiodothyronine concentration.

Adolescent↗
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↗
PubMed1973

Effects of replacement doses of sodium L-thyroxine on the peripheral metabolism of thyroxine and triiodothyronine in man.

Studies of the effect of L-thyroxine administration (0.3 mg daily for 7-9 wk) on the peripheral metabolism of (131)I-labeled triiodothyronine (T(3)) and (125)I-labeled thyroxine (T(4)) and on the concentration and binding of T(4) and T(3) in serum were carried out in 11 euthyroid female subjects. Administration of L-thyroxine led to consistent increases in serum T(3) concentration (137 vs. 197 ng/100 ml), T(3) distribution space (39.3 vs. 51.7 liters), T(3) clearance rate (22.9 vs. 30.6 liters/day) and absolute T(3) disposal rate (30 vs. 58 mug/day), but no change in apparent fractional turnover rate (60.3 vs. 60.6%/day). The proportion and absolute concentration of free T(3) also increased during L-thyroxine administration. Increases in serum total T(4) concentration (7.3 vs. 12.8 mug/100 ml) and in both the proportion and absolute concentration of free thyroxine also occurred. In five of the subjects, the kinetics of peripheral T(4) turnover were simultaneously determined and a consistent increase in fractional turnover rate (9.7 vs. 14.2%/day), clearance rate (0.84 vs. 1.37 liters/day), and absolute disposal rate (64.2 vs. 185.0 mug/day) occurred during L-thyroxine administration. Despite these increases in the serum concentration and daily disposal rate of both T(4) and T(3), the patients were not clinically thyrotoxic. However, basal metabolic rate (BMR) values were marginally elevated and, as in frank thyrotoxicosis, T(4)-binding capacities of thyroxine-binding globulin (TBG) and thyroxine-binding prealbumin (TBPA) reduced, suggesting that subclinical thyrotoxicosis was present. Thus, the often recommended replacement dose of 0.3 mg L-thyroxine daily may be greater than that required to achieve the euthyroid state. The studies have also provided additional evidence of the peripheral conversion of T(4) to T(3) in man and have permitted the calculation that approximately one-third of exogenously administered T(4) underwent deiodination to form T(3). To the extent that a similar fractional conversion occurs in the normal state, it can be calculated that a major fraction of the T(3) in serum derives from the peripheral deiodination of T(4) and that only a lesser fraction derives from direct secretion by the thyroid gland.

Adult↗