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Biomedical subjects

W L Green

Publications and source records attributed to W L Green.

12 recordsLinked to original sources
PubMed1992

Identification of thyroxine-sulfate (T4S) in human serum and amniotic fluid by a novel T4S radioimmunoassay.

Recently, we identified significant amounts of thyroxine sulfate (T4S) in fetal sheep serum, meconium, bile, and amniotic and allantoic fluids. Little is known, however, about sulfate conjugation of thyroxine in humans. In this study, we employed a novel, sensitive T4S RIA to address this question. The rabbit antiserum was quite specific; T4, T3, rT3, and 3,3'-T2 showed less than 0.002% cross-reactivity. Other analogs cross-reacted less than 0.0001%. Only rT3S and T3S cross-reacted significantly (9.9% and 2.0%, respectively). The mean serum T4S concentration (ng/dL) was 8.6 in euthyroid subjects, 14.4 in hyperthyroid subjects, 5.0 in hypothyroid subjects, 5.9 in pregnancy, and 4.5 in patients with nonthyroid illnesses. T4S concentration in amniotic fluid from women at 18-19 weeks of gestation (25.5 ng/dL) was higher than that at 14-15 weeks of gestation (14.3 ng/dL). A significant rise in serum T4S was detected in hyperthyroid patients 1 day after ingestion of 1 g of ipodate. These data suggest that T4S is a normal component of human serum and amniotic fluid, and it is mostly derived from T4 peripherally and accumulates when type I 5'-monodeiodinating activity is low in fetuses or inhibited by drugs, such as ipodate.

Amniotic Fluid↗
PubMed1991

Acute thyroid hormone promotes slow inactivation of sodium current in neonatal cardiac myocytes.

Sodium current (INa) inactivation kinetics in neonatal cardiac myocytes were analyzed using whole cell voltage clamp before and after acute treatments with thyroid hormone (3,5,3'-triiodo-L-thyronine, T3). In untreated neonatal myocytes, INa inactivation was predominantly mono-exponential, with 93 +/- 3% (S.D.; n = 9) of the peak amplitude decaying with a time constant, tau h1, of 1.8 +/- 0.5 ms at -30 mV. The remaining 7% of control INa decayed more slowly, with a time constant, tau h2, of 9.3 +/- 3.0 ms at -30 mV. The contribution of slowly-inactivating channels to peak current was increased from 7% to 43 +/- 27% within 5 min of exposure to 5-20 nM T3 (nine cells; P less than 0.005). The time constants for both the fast- and slow-inactivating components of peak current (tau h1 and tau h2) were not significantly changed by acute T3 treatment, nor was steady-state INa inactivation (h infinity) affected. Thyroid hormone action on sodium inactivation was partially reversible by lidocaine. These findings indicate that T3 acts at the neonatal cardiac cell membrane to promote slow inactivation kinetics in sodium channels.

Animals↗
PubMed1990

Acute effects of thyroid hormone on sodium currents in neonatal myocytes.

Sodium currents and action potentials were recorded from myocytes of neonatal rats during acute exposure to thyroid hormone (5-20 nM). One to 5 minutes after addition of thyroid hormone to the bath, decay from peak Na current was slowed, with the fractional current flowing 20 ms after onset (relative to peak current) increasing from 6 +/- 5% to 17 +/- 13% (p less than 0.01, n = 12). Action potential durations were increased from 55 +/- 14 to 86 +/- 36 msec (p less than 0.05, n = 6). The effects of thyroid hormone were partially reversed by lidocaine (60 microM, n = 5), a specific blocker of a slow sub-population of Na channels. Thus thyroid hormone interacts directly with myocyte membrane, probably by slowing of inactivation of Na channels.

Action Potentials↗
PubMed1978

Metabolism of thyroid hormones by rat thyroid tissue in vitro.

Rat thyroid lobes or hemilobes have been incubated in Krebs-Ringer phosphate buffer containing labeled T4 and/or T3, and the products were separated by paper chromatography. Labeled T4 was actively degraded; about half of the T4 metabolized was recovered as T3. Labeled T3 was also metabolized, but less rapidly than T4. Other than T3 produced from T4, the major products from both hormones were inorganic iodide and iodoprotein; the latter was presumably a secondary product of iodide organification because its formation was inhibited by hypoxia and methimazole. Feeding the animals a low iodine diet increased their hormone-metabolizing activity. Incubation under nitrogen did not affect the rate of T4 degradation, but partially inhibited T3 degradation. Degradation of both hormones was unchanged in the presence of methimazole and ascorbate, was markedly inhibited by 1 mM propylthiouracil (PTU), and was partially inhibited by azide and cyanide. Thyroid tissues concentrated both hormones, tissue to medium gradients averaging 5.4 for T4 and 20.7 for T3; none of the conditions affecting hormone degradation (incubation under nitrogen or with azide, cyanide, or PTU) significantly altered these gradients. It is concluded that the thyroid can metabolize both of its major hormones by a system distinct from thyroidal peroxidase. Hormone metabolism, therefore, is a potentially important factor in net hormone secretion. In its resistance to hypoxia, methimazole, and ascorbate and its sensitivity to PTU, the thyroid's system for generating T3 from T4 resembles T3-forming systems of liver and kidney. The thyroid, because T3 formation is its dominant pathway for T4 metabolism, may provide a useful model for study of this reaction.

Animals↗
PubMed1976

Thyrotropin levels in hyperlipidemic survivors of myocardial infarction.

In an earlier investigations, the prevalence of hyperlipidemia in a group of patients who survived myocardial infarction was determined, and family studies were performed to allow genetic classification of patients with hyperlipidemia. Radioimmunoassay for thyrotropin (TSH) has now been performed on plasmas from most of these hyperlipidemic survivors. Elevated TSH values were found in five of the 18 hyperlipidemic women over age 60, and in seven of the remaining 104 hyperlipidemic subjects. Among the various genetically defined types of hyperlipidemia, the highest prevalence of TSH elevations was seen in women with sporadic (nonfamilial) hypertriglyceridemia; four of the ten had an abnormal TSH level, and two of the remainder were receiving thyroid medication. Hypercholesterolemia was not strongly correlated with TSH abnormalities. These data support the hypothesis that clinically inapparent thyroid damage may be associated with coronary artery disease.

Female↗
PubMed1976

Induction of a coupling defect in rats during inhibition of tyrosine dehalogenase.

We have reported earlier that administration of 3-nitro-L-tyrosine (MNT), 8 mM in drinking water, to rats receiving a low iodine diet (LID) results in greater TSH secretion, larger goiters, and more rapid uptake and release of radioiodine than LID alone, and ultimately may produce hypothyroidism. These findings have been confirmed, and hypothyroidism documented by demonstrating depressed levels of hepatic mitochondrial alpha-glycerophosphate dehydrogenase. Also, prolonged treatment with MNT + LID produced a depression in labeled iodothyronine (ITh) synthesis, as judged by chromatographic analysis of thyroid digests from rats killed 4 or 24 hours after ip injection of radioiodine, or two weeks after adding radioiodine to drinking fluid. Low thyroidal ITh levels were accompanied by low levels of ITh in serum, despite the presence of various other labeled organic iodine compounds. Cessation of MNT treatment, or ip injection of small amounts (0.5-1.0 mug) of Na 127I together with radioiodine 4 h before sacrifice reversed the defect, and large amounts of ITh were found in both thyroid and serum. Labeled thyroprotein from MNT-treated rats showed increased susceptibility to disaggregation during freezing at pH 8.5; this abnormality was also reversed by stable iodine treatment. In glands labeled with radioiodine 24 h before sacrifice, stable iodine injection 20 h later was followed by increased thyroidal ITh. It is concluded that profound iodine deficiency, induced by MNT + LID, can lead to diminished ITh synthesis, or a "coupling defect". The results provide an explanation for the finding of low thyroidal ITh in patients with hereditary deficiency of tyrosine dehalogenase. The findings confirm an important role for iodine supply in ITh synthesis and thyroglobulin stability, and suggest that rats treated with MNT + LID provide a model for study of the effects of extreme iodine deficiency.

Animals↗
PubMed1976

Triiodothyronine (T3)-binding immunoglobulins in a euthyroid woman: effects on measurement of T3 (RIA) and on T3 turnover.

A 36-year-old woman with nodular goiter, nervousness, and tachycardia was evaluated for T3 toxicosis. Her serum thyroxine level, resin T3 uptake, and thyroidal radioiodine uptake were normal. Her T3 (RIA), by a technique employing charcoal to separate bound and free T3, was reported as indeterminate due to an interfering substance; by a double-antibody method, her T3 (RIA) was 325 ng/dl. Further studies of the patient's serum revealed an abnormal T3-binding protein which misgrated in the beta-gamma globulin zone on paper electrophoresis and gel filtration chromatography (Sephadex G-200), and was precipitated from serum by rabbit anti-human Fab antibody. The gamma globulin fraction of the patient's serum, separated by a standard technique, showed strong binding activity toward [125I]T3, with an association constant of 4.1 X 10(8) 1/mole (Scatchard plot). In a similar system, labeled T4 was not bound. To avoid artefacts which this T3-binding protein might produce in assaying unextracted serum, T3 (RIA) was performed on an ethanol extract of serum and found to be 191 ng/dl, a slight elevation. However, the metabolic clearance rate of injected [125I]T3, estimated by non-compartmental analysis of the serum decay curve or by the specific activity or urinary T3, was about 16 1/day, a low value, so that the T3 production rate, 31 mug/day, was normal. The patient's symptoms disappeared with the resolution of domestic problems, and she appeared clinically euthyroid. Serum TSH was 5.0 uU/ml and antithyroglobulin titer, 1:16. A test for antibodies to thyroid microsomes was negative. We postulate that this subject was euthyroid, but had a concentration of T3-binding immunoglobulin which was sufficient to produce modest slowing of T3 turnover, borderline elevation of extractable T3 (RIA), and a major artefact in the T3 (RIA) measurement of unextracted serum. A similar abnormality may account for other instances of high T3:T4 ratios in serum.

Adult↗
PubMed1975

Metabolism of thyroxine and triiodothyronine in patients with chronic granulomatous disease.

Normal human leukocytes can degrade thyroid hormones in vitro especially during phagocytosis. To test whether the leukocyte system plays a significant role in hormone economy in vivo, studies of the metabolism of labeled T4 and T3 granulomatous disease, whose leukocytes had earlier been shown to have a reduced ability to degrade the thyroid hormones. Hormone turnover rates in the 3 subjects were similar to those reported for normal children by various investigarors. Also, normal ratios between fecal and urinary excretion of radioactivey were observed, suggested that deiodination was the major route of hormone breakdown, as it is in normal subjects. Our interpretations of these findings are: 1) an intact leukocyte hormone degrading system is not essential for normal rates of thyroid hormone metabolism in vivo; 2) the leukocyte defect in chronic granulomatous disease is not accompanied by a general defect in mechanism for thyroid hormone degradation in other tissues.

Adolescent↗