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Biomedical subjects

R D Utiger

Publications and source records attributed to R D Utiger.

At least 91 records · Page 5Linked to original sources
PubMed1978

Failure of alpha-methyltyrosine to inhibit peripheral triiodothyronine formation.

To determine if the adrenergic nervous system, and specifically tyrosine hydroxylase, plays a role in the extrathyroidal conversion of T4 to T3, normal male volunteers were treated with T4 and subsequently with T4 and alpha-methyl-p-tyrosine (alpha-MPT), an inhibitor of tyrosine hydroxylase, for 2 weeks. The mean serum T4 and T3 concentrations increased during T4 administration and remained at the same levels during combined T4 and alpha-MPT administration. Urinary vanillylmandelic acid excretion declined significantly during alpha-MPT administration. These results do not support the hypothesis that tyrosine hydroxylase is involved in extrathyroidal T3 production.

Adult↗
PubMed1977

Subcellular distribution of thyrotropin-releasing hormone (TRH) in rat brain and hypothalamus.

TRH localization in rat brain and hypothalamic tissue was studied by determination of immunoassayable TRH in subcellular fractions prepared from homogenates of these tissues. In both hypothalamus and brain, most of the TRH was found in a crude mitochondrial fraction and its concentration was higher in the synaptosomal fraction isolated by density gradient centrifugation. Electron microscopy was used to verify the composition of the fractions. Exposure of the brain crude mitochondrial fraction to osmotic shock resulted in solubilization of TRH which then was sedimented by centrifugation at 96,000 X g. TRH added to brain homogenates in vitro was rapidly destroyed by incubation at 37 degrees C, but no endogenouse TRH was lost by such incubation. The localization of TRH of hypothalamic and brain tissue to subcellular fractions consisting largely of synaptosomes and synaptic vesicles is compatible with a neurotransmitter function for this substance.

Animals↗
PubMed1977

Acute effect of inorganic iodide after 131I therapy for hyperthyroidism.

Patients treated with inorganic iodide weeks to years following 131I therapy for hyperthyroidism do not adapt to its antithyroid effect. To determine whether such adaptation occurs soon after 131I therapy, serum thyroxine (T4) and triiodothyronine (T3) concentrations were measured daily for 9-14 days following 131I therapy in seventeen hyperthyroid patients. Nine patients received 150 mg KI daily starting 48 h after 131I administration; eight received only 131I. Serum T4 and T3 concentrations did not change significantly in the patients who received only 131I. In the patients who received 131I and KI, serum T4 and T3 concentrations fell promptly, reaching nadir values 2-10 days after initiation of iodide, and then increased despite continuation of KI therapy. The mean maximal fall in serum T4 was 34% and in serum T3 42%. These results show that "escape" from the acute anti-thyroid effect of iodide occurs when it is given immediately after 131I therapy, thus limiting the utility of iodide as a therapeutic agent at this time.

Adolescent↗
PubMed1977

Triiodothyronine in rat submaxillary salivary gland: effects of altered adrenergic function.

To determine whether changes in adrenergic nerve terminal activity may influence tissue metabolism of iodothyronines, sympathetic nervous function of the rat submaxillary salivary gland was altered, and effects on salivary gland triiodothyronine (T3) uptake and retention measured. Following unilateral superior cervical ganglionectomy, denervated salivary gland contained 24% less (p less than 0.02) radioimmunoassayable T3/mg and took up 20% less (p less than 0.001) intravenously administered 125I-T3/mg than the contralateral innervated gland. Effects were similar at 7, 14 and 56 days following ganglionectomy and could not be accounted for by post-denervation changes in the delivery of the isotope, in total salivary gland water, in vascular volume or in extracellular or intracellular fluid spaces. When reserpine was administered to unilaterally ganglionectomized animals, uptake of 125I-T3/mg in the innvervated gland was reduced by 10% (p less than 0.005), relative to the denervated gland. The results suggest that loss or diminution of peripheral adrenergic nerve terminal activity reduces tissue uptake and retention of T3.

Animals↗
PubMed1977

Thyrotropin-releasing hormone content of rat brain and hypothalamus: results of endocrine and pharmacologic treatments.

Studies of hypothalamic and regional brain TRH content in the rat after administration of various hormonal and pharmacologic agents were performed. No consistent changes in TRH content in the hypothalamus or brain followed thyroidectomy, hypophysectomy or administration of thyroxine or dexamethasone. There was a significant fall in hypothalamic forebrain and brain stem TRH content 60 min after insulin administration and in brain stem TRH at 30 and 120 min as well. Administration of alpha-methyl-paratyrosine, parachlorophenylalanine or reserpine, in varying doses and for varying periods, did not alter hypothalamic or regional brain TRH content. Thus, little evidence that hypothalamic or brain TRH content is dependent on hormonal milieu or neurotransmitter content was found.

Animals↗
PubMed1977

Immunoreactivity and serum destruction of N3immethyl-trh.

Pyroglu-N3immethyl-histidyl-prolineamide (MeTRH) is a more potent stimulator of thyrotropin and prolactin secretion than thyrotropin-releasing hormone (TRH). In this study, the immunoreactivity of MeTRH and its susceptibility to destruction by serum were investigated. When tested in radioimmunoassays employing four different anti-TRH sera. MeTRH had 25 to 60% of the immunoreactivity of TRH. Serum destroyed theimmunoreactivity of MeTRH at one-half of the rate at which TRH was destroyed. Slow degradation alone would not appear to explain the potency of MeTRH.

Antigen-Antibody Reactions↗
PubMed1977

Serum thyroxine-binding globulin: determination by competitive ligand-binding assay in thyroid disease and pregnancy.

Serum thyroxine-binding globulin (TBG) concentrations were measured by competitive ligand-binding assay in normal subjects and patients with a variety of abnormalities of thyroid hormone production or TBG production. The mean serum TBG concentration in 73 normal adults was 3.4 +/- 0.6 mg/100 ml. No correlations with age, sex or serum thyroxine (T4) or triiodothyronine (T3) concentrations were found. Serum TBG concentrations were normal in patients with hyperthyroidism. They were significantly elevated in hypothyroid patients, and fell to normal with thyroxine treatment. In pregnant women, serum TBG concentrations were markedly increased, being 7.1 +/- 1.2 (mean +/- SD) mg/100 ml in women in their first trimester, 9.0 +/- 1.0 mg/100 ml in the second trimester and 8.9 +/- 1.6 mg/100 ml in the third trimester. There was a positive correlation between serum TBG concentration and both serum T4 and serum T3 concentrations in pregnant women. Competitive ligand-binding assay is a simple and reliable method for TBG asay and yields results similar to those of electrophoretic saturation techniques.

Acromegaly↗
PubMed1977

Thyroidal and peripheral production of thyroid hormones. Review of recent findings and their clinical implications.

There are two biologically active thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Most T3 is produced extrathyroidally, so that alterations in circulating thyroid hormone concentrations may occur as a result of both thyroidal and extrathyroidal abnormalities. Extrathyroidal T4 conversion to T3 is decreased in patients with different acute and chronic illnesses. When T4 conversion to T3 is impaired and serum T3 concentrations decline, serum concentrations of biologically inactive 3,3',5'-triiodothyronine (reverse T3) increase. In this review, we present current information on thyroidal and extrathyroidal T4 and T3 production in normal subjects and patients with various thyroid diseases and other illnesses, consider the physiologic significance of these changes, and discuss the value and interpretation of various iodothyronine measurements.

Chemical Phenomena↗
PubMed1976

Pituitary-thyroid regulation in euthyroid patients with Graves' disease previously treated with antithyroid drugs.

To understand why some patients with hyperthyroidism due to Graves' disease remain euthyroid after a course of antithyroid drug therapy, pituitary-thyroid regulation was studied in 20 such patients who had remained well for six months or longer after the withdrawal of antithyroid drugs. Only patients who were clinically euthyroid and had normal serum thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) concentrations were studied. Serum TSH responses to thyrotropin-releasing hormone (TRH) and thyroid suppression were determined in all patients. Seven patients had normal responses to both tests. Six patients had a subnormal response to TRH and abnormal suppression. Five patients had a subnormal response to TRH and normal suppression, and two patients had a normal TSH response to TRH and abnormal suppression. There were no differences in the mean serum T4, T3 or TSH concentrations between any of the groups. The mean duration of time after antithyroid drug withdrawal was 19 months in the patients in whom both tests were abnormal, whereas it was 58 months in those in whom both tests were normal and 45 months in those with a subnormal TSH response to TRH and a normal suppression test. Thus, in 13 of the 20 patients studied, various degrees of abnormality of pituitary-thyroid regulation were demonstrable. These results suggest that, in most patients with Graves' disease who remain clinically and biochemically euthyroid after a course of antithyroid drug therapy, the disease persists in a mild or subclinical form.

Adolescent↗
PubMed1976

Changes in serum thyrotropin (TSH) in man during halofenate administration.

Halofenate, a serum lipid-lowering agent which inhibits binding of thyroid hormone to thyroxine-binding globulin (TBG), was administered daily for 14 days to 8 hypothyroid subjects with elevated TSH concentrations as a result of incomplete thyroxine (T4) therapy. Drug administration resulted in mean increases in serum dialyzable fraction T4 (DFT4) of 52% over pretreatment levels (P less than 0.01) and in dialyzable fraction triiodothyronine (DFT3) of 26% in 7 subjects, (P less than 0.01). During halofenate treatment in these 7 subjects, serum TSH concentrations decreased significantly (mean = 39%, P less than 0.01) when DFT4 and DFT3 were increased by halofenate. In only two subjects was there a convincing temporal relationship between increased serum absolute free T4 (AFT4) and decreased serum TSH concentrations. Contrary to what would be predicted from the "free hormone hypothesis", changes in serum TSH concentration in these hypothyroid patients appeared to relate primarily to changes in the free fraction of circulating T4 and T3 (DFT4, DFT3), rather than to alterations in AFT4 or AFT3. Halofenate did not alter serum TBG binding capacity. An eighth subject did not show increased DFT4 and DFT3 during halofenate treatment despite achievement of therapeutic serum levels of the agent; in this patient, serum TSH levels rose progressively throughout the period of inadequate T4 replacement and halofenate administration. In hypothyroid patients, short-term halofenate use suggests that the pituitary-thyroid hormone feedback circuit can respond to increases in serum DFT4 and DFT3 in the absence of detactable increases in absolute free hormone concentrations.

Adult↗
PubMed1976

Thyroid function and metabolic state in chronic renal failure.

Thirty-eight patients with chronic renal insufficiency who were in a dialysis program underwent studies of thyroid function and metabolic status. Mean values for serum total and free thyroxine (T4) concentrations and thyroxine-binding globulin capacity were within normal limits. Although mean serum total triiodothyronine (T3) concentration was normal, 43% of the group had low serum T3 and 54% had low serum free T3 concentrations. Serum thyrotrophin (TSH) concentrations were normal in all but four subjects who had very slight elevations. Metabolic status was assessed by various metabolic tests; mean values for each of these tests were normal, and the clinical index scores indicated that all patients were euthyroid. Results of metabolic testing were similar in patients with low and those with normal serum T3 concentrations. Low serum T3 measurements did not accurately reflect metabolic state in patients with chronic renal failure, whereas serum free T4 and TSH concentrations were reliable indicators of thyroid state.

Adolescent↗
PubMed1975

Effect of hypothalamic deafferentation on thyrotropin-releasing hormone levels in rat brain.

The medial basal hypothalamus was isolated from the remainder of the brain of the rat using a Halász knife. Ten to 14 days after the surgical procedure the concentration of thyrotropin-releasing hormone within the island of hypothalamic tissue was 76% lower than in tissue from sham-operated control rats. Thus, much of the thyrotropin-releasing hormone that is normally present in the medial basal hypothalamus may be synthesized by cells outside of this region. There were no reductions in hormone levels in regions outside of the hypothalamic island after the surgical procedure. Extrahypothalamic thyrotropin-releasing hormone does not appear to be produced by hypothalamic neurosecretory cells.

Animals↗
PubMed1975

Reduction in extrathyroidal triiodothyronine production by propylthiouracil in man.

To determine if propylthiouracil (PTU) inhibited extrathyroidal thyroxine (T4) to triiodothyronine (T3) conversion in man, PTU was administered to T4-treated hypothyroid patients and serial measurements of T4, T3, and thyrotropin (TSH) carried out. All patients had proven thyroidal hypothyroidism and had been receiving 0.1 or 0.2 mg T4 daily for at least 2 mo before study. Hormone measurements were made for 5 consecutive days before and daily during a 7-day treatment period with PTU, 1,000 mg/day. In eight patients receiving 0.1 mg T4 daily, administration of PTU resulted in a prompt fall in mean serum T3 concentrations from 78 plus or minus 6 ng/100 ml (SEM) to 61 plus or minus 3 ng/100 ml after 1 day. The mean serum T3 concentrations ranged from 55 to 60 ng/100 ml during the remainder of the PTU treatment period (P less than 0.01). The mean control serum TSH concentration was 29.6 muU/ml and it increased to a peak of 40 muU/ml on the 5th and 6th days. In five patients receiving 0.2 mg T4 daily, the mean control serum T3 concentration was 84 plus or minus 7 NG/100ML. It fell to 70 plus or minus 5 ng/100 ml after 1 day and 63 plus or minus 7 ng/100 ml after 2 days of PTU administration and thereafter ranged from 6) to 69 ng/100 ml (P LESS THAN 0.01). Serum TSH concentrations did not increase. No changes in serum T4 concentrations were found in either group. In five patients who received 100 mg methimazole (MMI) daily for 7 days there were no changes in serum T4, T3, or TSH concentrations. These results indicate that PTU, but not MMI, produces a prompt and sustained, albeit modest, reduction in serum T3 concentrations in patients whose sole or major source of T3 is ingested T4. These findings most likely result from inhibition of extrathyroidal formation of T3 from T4.

Administration, Oral↗
PubMed1975

Plasma thyrotropin-releasing hormone concentrations in the rat. Effect of thyroid excess and deficiency and cold exposure.

To investigate the physiology of thyrotropin-releasing hormone (TRH) secretion from hypothalamus and brain, a method for measurement of peripheral plasma TRH concentrations in rats was developed. Blood was collected in heparin and dimercaptopropanol containing [3H]TRH to determine recovery. The plasma was extracted with methanol and the redissolved dried methanol extracts applied to anti-TRH Sepharose columns. These columns bound greater than 80% of 125I-TRH applied and had a capacity in excess of 20 ng TRH. TRH was eluted from the anti-TRH Sepharose with acetic acid and quantitated by radioimmunoassay of the lyophilized acetic acid eluate. Mean recovery of unlabeled TRH was 44.7+/-6.1% (SD) and mean recovery of [3H]TRH was 44.0+/-4.0%. Mean plasma TRH concentrations, corrected for recovery, in plasma pools from eight groups of normal male rats (four to seven pools/experiment, five to seven rats/pool) ranged from 7 to 30 pg/ml (mean, 16). In experiments in which rats were given 5, 10, 15, 0r 50 mug thyroxine daily for 1 wk or in thyroidectomized rats, mean plasma TRH concentrations did not differ significantly from those of control animals sacrificed at the same time. In each experiment, four to seven plasma pools, each from five to seven rats, were processed from both control and experimental groups. No changes in plasma TRH concentrations were found in rats exposed to cold (4degreeC) for 30, 60, and 90-180 min. Signigicant increases in plasma thyrotropin (TSH) concentrations were found in all cold-exposed animals. These results provide no evidence that thyroid hormone excess of deficiency affects TRH secretion. If TRH secretion is responsible for cold-induced increases in plasma TSH concentrations, the increase in TRH secretion is of insufficient magnitude to alter periperal plasma TRH concentrations.

Animals↗