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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyrotrophin-releasing hormone (TRH), like several other neuropeptides, has been detected in the gastro-intestinal tract of adult rats. More recently, elevated concentrations of TRH have been found in the neonatal rat pancreas. This study was undertaken to evaluate pancreatic TRH degrading activity (TRH-DA) in infant rats from birth until adult life. Pancreatic TRH of age-matched rats was also measured by radioimmunoassay. TRH-DA was present in normal adult rat pancreas; though absent at birth and in the early postnatal period up to day 7, this activity was detected during the remainder of the developmental period. TRH content (pg +/- SEM per pancreas) was 1139 +/- 88 on day 1, reached a peak value of 7360 +/- 758 at day 2 and then decreased steadily to adult level. TRH-DA has been found to be present at birth in hypothalamus and liver but not in plasma. The developmental patterns of TRH-DA in plasma and in pancreas were parallel and seem to be thyroid hormone dependent. The absence of TRH-DA in the neonatal pancreas may also be related to the high TRH concentrations detected in this organ during the neonatal period.
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PMID:Developmental pattern of TRH-degrading activity and TRH content in rat pancreas. 642 13

This study was undertaken to investigate the changes in carnitine metabolism in rats and mice injected with T4 for 3 days and 10 days, respectively, and in rats fed a T3 and T4-supplemented diet for 6 weeks. Thyroid hormone administration brought about a significant increase in urinary excretion of total carnitine. In T3 + T4-treated rats urinary esterified-carnitine to free-carnitine ratio increased significantly in the later phase of administration. Carnitine pool size in the body was significantly decreased in both T4-injected mice and T3 + T4-fed rats. In the latter animals, this decrease was due to the reduced carnitine contents in organs other than the liver, especially in skeletal muscle. The amount of carnitine synthesized by control and T3 + T4-treated rats was calculated from the data on carnitine intake, urinary carnitine excretion and carnitine pool size in the body over the 6-week period. Values obtained were 66.2 +/- 3.2 (mean +/- SEM) mumol/rat and 28.5 +/- 4.9 mumol/rat, respectively, and the difference was significant (p less than 0.05). These results indicate that carnitine synthesis is depressed by thyroid hormone, however, some possibilities that thyroid hormone may increase carnitine synthesis were also discussed.
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PMID:Carnitine metabolism in thyroid hormone treated rats and mice. 664 85

Earlier studies have shown larger increments in serum T3 in 2-week-old congenitally hypothyroid rats than in euthyroid controls after injections of small doses of T4. Since hepatic and renal 5'-deiodination of T4 to T3 in vitro (5' D-I) is reduced during the neonatal period and in hypothyroidism, those results suggest that there may be major changes in the distribution and metabolism of T3 or that an alternative enzymatic pathway is the predominant source of extrathyroidally produced T3 in these rats. The alternative pathway, 5' D-II, is a relatively minor source of serum T3 in adult euthyroid rats, but the contribution of this pathway to the extrathyroid T3 pool during the neonatal period and in hypothyroxinemia is not known. Consequently, we studied [125I]T4 and [131I]T3 kinetics and fractional T4 to T3 conversion in 2-week-old euthyroid and hypothyroid rats and then explored the source of circulating T3 by manipulating 5' D-I activity with propylthiouracil and that of 5' D-II with thyroid hormone. The plasma clearance rate of T4 was increased in hypothyroid rats, a difference entirely accounted for by the faster fractional rate of irreversible removal in the hypothyroid pups. Plasma clearance rate of T3 was reduced in hypothyroid rats owing to the reduced volume of distribution of T3. Fractional T4 to T3 conversion was 2- to 3-fold higher in euthyroid or hypothyroid neonates than in adult rats. In euthyroid rats the serum concentration of T4 was 36 +/- 1 (SEM) ng/ml and that of T3 0.61 +/- 0.03 ng/ml, and the production rates were 432 and 159 ng day-1 30 g-1 BW for T4 and T3, respectively. About 80% of the T3 in euthyroid neonates was produced extrathyroidally . These findings are inconsistent with hepatic and renal 5' D-I being the main source of serum T3 in 2-week-old rats. In fact, liver and kidney 5' D-I activities were 40% and 65% of the corresponding adult values in euthyroid neonates, and in hypothyroid pups were further reduced to 15% and 17%. In contrast, 5' D-II, previously reported to be high in central nervous tissue and pituitary, was 7-10-fold higher in brown adipose tissue (BAT) of hypothyroid pups than in that of euthyroid ones.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Thyroid hormone metabolism and the source of plasma triiodothyronine in 2-week-old rats: effects of thyroid status. 672 86

The effects of a daily oral dose (1.4 mg) of 3,5,3'-Triiodothyroacetic acid (Triac) on thyroid hormone levels (T4, T3 and rT3) and on the TSH and PRL responses to TRH were studied in 15 normal subjects and 5 hypothyroid patients. There were no significant changes in weight, heart rate, reflex time, or serum concentration of either cholesterol or triglycerides after 6 weeks of Triac administration. However, T4 was significantly reduced to a lower mean level (mean +/- SEM, 7.3 +/- 0.7 to 4.3 +/- 0.6 microgram/dl) in the control group. T3 and rT3 concentrations increased, possibly due to a cross-reaction with Triac in their respective RIAs. The peak TSH response to TRH in the normal subjects was 17.6 +/- 3.4 muU/ml and fell significantly to 2.0 +/- 0.8 muU/ml after Triac administration. In the hypothyroid subjects the mean serum TSH level was significantly reduced from 136 +/- 66 to 12.6, 10.5, and 11.6 muU/ml in the weeks after Triac administration. The mean peak response of both TSH and PRL after TRH (206 muU and 44.8 ng/ml, respectively) declined significantly to 63.4 muU/ml and 24 ng/ml. It was concluded that this dose of Triac partially inhibits the synthesis and secretion of TSH and PRL without any major peripheral metabolic effects.
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PMID:Triac (3,5,3'-triiodothyroacetic acid) partially inhibits the thyrotropin response to synthetic thyrotropin-releasing hormone in normal and thyroidectomized hypothyroid patients. 676 60

The main objective of this study was to determine whether the principal abnormality of thyroid function observed in patients with chronic renal failure, low serum triiodothyronine (T(3)) concentration, causes hypothyroidism at the tissue level. A partially nephrectomized (Nx) uremic rat model was developed and the following parameters of thyroid function were assessed: serum total thyroxine (TT(4)), total T(3) (TT(3)), and thyrotropin and liver T(3) content, and activity of two thyroid hormone-dependent enzymes, mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) and cytosol malate dehydrogenase (MDH). The results were compared to those of intact control (C), thyroidectomized (Tx), and nephrectomized-thyroidectomized (NxTx) littermates.Results expressed as mean+/-SEM showed that Nx rats had a fivefold increase in blood urea nitrogen, (112+/-20 mg/dl in Nx, and 22+/-1 mg/dl in C) and manifested all the changes of of thyroid function observed in uremic men, including a low serum TT(3) level (30+/-7 ng/dl in Nx and 50+/-6 ng/dl in C). In the liver, T(3) was significantly reduced (18+/-2 ng/total liver in Nx and 35+/-3 ng/total liver in C) as well as the activities of alphaGPD (8.8+/-1.0 and 16.1+/-1.5 DeltaOD/min per total liver in Nx and C, respectively) and MDH (6.3+/-1.6 and 12.6+/-2.2 U/total liver in Nx and C, respectively). The reduction in liver enzyme activities correlated significantly with the decrease in T(3) content. The changes in Tx rats were as expected, showing a profound reduction in serum hormone levels, liver T(3) content, and liver enzyme activities. Serum thyrotropin was markedly elevated to 2,390+/-212 ng/ml as compared to 703+/-61 in C and 441+/-87 ng/ml in Nx rats. The NxTx rats showed the combined effects of nephrectomy and thyroidectomy; blood urea nitrogen was elevated to 203, and serum levels of TT(4), TT(3), and thyrotropin were 0.4, <10, and 2,525, respectively. Total liver T(3) and alphaGPD and MDH were strikingly low; the corresponding values were 3.5, 2.4, and 2.5.l-triiodothyronine replacement (0.4 mug/100 g body wt/d) for 4 wk in the Nx rats resulted in significant increases in liver enzyme activities, alphaGPD and MDH rose by 70 and 60% over their respective basal values without alteration in the severity of azotemia. From these data, we conclude that the reduction of liver T(3) content in the uremic rats, accompanied by a decrease in alphaGPD and MDH activity, indicates the presence of hypothyroidism at the tissue level. Restoration of enzyme activities toward normal levels after T(3) administration provided further supporting evidence that the diminution in liver enzyme activity was causally related to tissue T(3) deficiency.
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PMID:Thyroid function in a uremic rat model. Evidence suggesting tissue hypothyroidism. 677 47

To study whether there is an association between hypertension and hypothyroidism, measurements of blood pressure and thyroid function were determined in 477 female patients with chronic thyroiditis. Based on the blood levels of thyroxine (T4) and thyroid stimulating hormone (TSH), 308 patients were considered euthyroid and 169 were hypothyroid [T4 = 2.9 +/- 0.1 micrograms/dl and TSH = 105.8 +/- 6.8 microU/ml (mean +/- SEM)]. Diastolic, but not systolic, blood pressure in hypothyroid patients over 50 years was higher than in euthyroid patients of corresponding age groups. The prevalence of hypertension was higher in hypothyroid patients when hypertension was defined as the systolic and/or diastolic blood pressure above 160/95 mm Hg (14.8% vs 5.5%; p less than 0.01). Correlations between diastolic, but not systolic, blood pressure and either the blood level of triiodothyronine (T3) or T4 was significant (r = - 0.174, p less than 0.01, and r = 0.208, p less than 0.01, respectively) when data from both euthyroid and hypothyroid patients were combined. Adequate thyroid hormone replacement therapy for an average 14.8 months in 14 patients resulted in a normalization of thyroid function and a reduction of blood pressure (p less than 0.01). In four who showed no change in thyroid function due to inadequate replacement therapy, blood pressure remained elevated. These results suggest a close association between hypertension and hypothyroidism.
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PMID:Hypothyroidism as a cause of hypertension. 684 58

Administration of the anti-inflammatory drug fenclofenac (600 mg bd) for 28 days to four females with thyrotoxicosis resulted in a rapid decline in thyroid hormone levels. The mean total thyroxine (T4) level of 173 +/- 8.6 (SEM) nmol/l before therapy was normalized to 70 +/- 6.4 nmol/l after administration of the drug for 7 days. Free T4 levels also decreased significantly but not to within the reference range in all subjects. Mean total triiodothyronine (T3) and reverse T3 levels declined from 6.2 +/- 0.9 nmol/l and 0.63 +/- 0.2 nmol/l respectively before therapy to 3.8 +/- 0.5 nmol/l and 0.52 +/- 0.1 nmol/l after 7 days' treatment but remained consistently elevated in all subjects. Clinical thyroid status remained unchanged despite these marked reductions in circulating thyroid hormone levels, suggesting that fenclofenac was of no therapeutic benefit.
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PMID:Biochemical and clinical effects of fenclofenac in thyrotoxicosis. 704

The reported failure of serum TSH to rise in response to the low serum T3 of severe systemic illness may be due to the known stress inhibition of TSH secretion. We therefore measured TSH and total and free thyroid hormones during the course of recovery from severe illness. During recovery, TSH increased at a time when T3 was rising but still below normal (mean TSH during recovery, 6.5 +/- 0.8 SEM microU/ml, n = 41 vs. normal, 2.5 +/- 0.2 SEM microU/ml; n = 31; P less than 0.001), TSH concentrations were negatively correlated with total and free T3 and less strongly correlated with total T4 but not with free T4. Average TSH concentrations were also significantly elevated in severely ill patients with hypothermia that was unrelated to cold exposure (mean TSH, 5.6 +/- 1.3 microU/ml; n = 11; P less than 0.005). The T3 concentrations in these sera were lower than those of other severely ill patients. Thus, during recovery from severe illness and during hypothermia not induced by cold, the relationship between serum T3 and TSH is qualitatively similar to that seen in primary hypothyroidism and may imply a pituitary response to a deficiency of thyroid hormone.
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PMID:The relationship between serum triiodothyronine and thyrotropin during systemic illness. 707 98

The TRH test, using synthetic TRH (TSH-releasing hormone) is the most sensitive test for the assessment of thyroid function. It may show elevated basal TSH and/or an exaggerated TSH response to TRH, despite normal thyroid hormone levels (T4, FT4I, T3). This condition is termed "preclinical hypothyroidism" (pc hypo). Thyroid hormone levels, the clinical index of Billewicz and metabolic impact on target tissues were studied prospectively in 38 pc hypo women and compared with 20 controls matched for age, weight and sex and 9 patients with overt hypothyroidism. For metabolic evaluation at the tissue site two new metabolic tests were developed and standardized, the systolic time intervals (STI) and sex-hormone-binding globulin (SHBG), which were used in conjunction with the ankle reflex time (ART) and lipids (cholesterol and triglycerides). The thyroid hormones T4, FT4I and T3 in pc hypo (77.8 +/- 2.0 nmol/l; 71.8 +/- 2.3; 1.92 +/- 0.07 nmol/l respectively; mean +/- SEM) were within the normal range (by definition), but significantly lower in comparison with the normal controls (105.5 +/- 3.3 nmol/l; 97.8 +/- 3.1; 2.91 +/- 0.12 nmol/l respectively; p less than 0.001). The clinical index and metabolic parameters SHBG and ART showed significant hypothyroid changes. STI (measured as preejection period) and lipids were not yet significantly different from the controls despite a hypothyroid tendency in many single individuals. The etiology in 144 patients with pc hypo (out of 2969 TRH tests) was analysed and the following causes identified: a) treated hyperthyroidism (38 after radioiodine, 5 after partial thyroidectomy, 5 after antithyroid drugs, 5 after radioiodine and partial thyroidectomy); b) simple goiter (7 without and 21 after partial thyroidectomy); c) autoimmune thyroiditis (27); d) other causes such as subacute thyroiditis (10); Riedel's thyroiditis (2), dyshormogenesis (2), drugs (6), treated toxic adenomas (2); e) etiology unknown or not identified (14).
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PMID:[Metabolic evaluation and etiology of "preclinical hypothyroidism": a preliminary report]. 719 52

To explore the control of thyroid hormone metabolism in brain during maturation, we have measured iodothyronine deiodination in homogenates of rat cerebrum, cerebellum, and hypothalamus from 1 d postnatally through adulthood. Homogenates were incubated with (125)I-l-thyroxine (T(4)) + [(131)I]3,5,3'-l-triiodothyronine (T(3)) + 100 mM dithiothreitol. Nonradioactive T(4), T(3), and 3,3',5'-triiodothyronine (rT(3)) were included, as appropriate. The net production rate of [(125)I]T(3) from T(4) in 1-d cerebral homogenates was similar to the rate in adult cerebral homogenates (9.9+/-2.5[SEM]% vs. 8.9+/-1.2% T(4) to T(3) conversion in 2 h). Production of T(3) was not detectable in 1-d cerebellar and hypothalamic homogenates. The net T(3) production rate in adult cerebellar homogenates was twice as great as, and that in adult hypothalamic homogenates similar to, the rate in cerebral homogenates. Tyrosyl ring deiodination rates of T(4) and T(3) were more than three times as great in cerebral homogenates from 1-d-old rats as in adult cerebral homogenates. In cerebellar homogenates from 1-d-old rats, tyrosyl ring deiodination rates were much greater than the rates in adult cerebellar homogenates, but less than those in 1-d cerebral homogenates. In 1-d hypothalamic homogenates, tyrosyl ring deiodination rates were the highest of all the tissues tested, whereas rates in adult hypothalamic homogenates were similar to those in adult cerebral homogenates. During maturation, T(4) 5'-deiodination rates increased after 7 d and exceeded adult rates between 14 and 35 d in cerebral and cerebellar homogenates, and at 28 and 35 d in hypothalamic homogenates. In cerebral homogenates, the peak in reaction rate at 28 d reflected an increase in the maximum enzyme activity (V(max)) of the reaction. T(4) and T(3) tyrosyl ring deiodination rates decreased progressively with age down to adult rates, which were attained at 14 d for cerebrum and cerebellum and at 28 d for hypothalamus. These studies demonstrate quantitative differences in T(4) 5'-deiodinase activities in cerebrum, cerebellum, and hypothalamus at all ages, with the overall maturational pattern differing from the developmental patterns of both the pituitary and hepatic T(4) 5'-deiodinases. Iodothyronine tyrosyl ring deiodinase activities also vary quantitatively among these same brain regions and exhibit a pattern and a time-course of maturation different from that of the T(4) 5'-deiodinase. These enzymes could have important roles in the regulation of intracellular T(3) concentrations and, hence, on the expression of thyroid hormone effects.
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PMID:Maturational patterns of iodothyronine phenolic and tyrosyl ring deiodinase activities in rat cerebrum, cerebellum, and hypothalamus. 720 75


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