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Biomedical subjects

P Laurberg

Publications and source records attributed to P Laurberg.

At least 73 records · Page 4Linked to original sources
PubMed1989

Paradoxically subnormal serum T4 and T3 in dogs after prolonged excessive TSH stimulation of the thyroid caused by post-cAMP refractoriness of thyroid hormone secretion.

Several studies have demonstrated that excessive TSH stimulation of the thyroid for hours to days makes the thyroid gland less responsive to TSH. In this study we extended the period of excessive TSH stimulation of dog thyroids in vivo to 28 days. Serum T4 and T3 were considerably elevated initially but then gradually declined and became paradoxically subnormal after 3 weeks. This was not caused by production of TSH antibodies. At day 28 the thyroid lobes were perfused for measurements of T4 and T3 secretion. Both the basal secretion rate and the response to TSH were considerably lower after TSH pretreatment than in control dogs. This was not due to reduction of TSH receptors because the response to forskolin was similarly reduced. The cAMP response to TSH and forskolin was not blunted by TSH pretreatment. The total amount of thyroglobulin in the thyroid was not significantly altered by TSH pretreatment, but the T4, T3, and iodine content of thyroglobulin was reduced to 50% to 70% of control levels. Such a moderate reduction in hormone content could not explain the development of subnormal serum T4 and T3 during intensive TSH stimulation. Apparently one or more processes involved in thyroid hormone secretion after cAMP generation were made so refractory to TSH by the prolonged excessive stimulation, that a state of biochemical hypothyroidism developed.

Animals↗
PubMed1989

Rat heart thyroxine 5'-deiodinase is sensitively depressed by amiodarone.

Thyroxine 5'-deiodinase activity (5'-D) is depressed in rat liver by amiodarone. To investigate the possible tardive effect of amiodarone on 5'-D in different tissues, rats were fed amiodarone according to a short-term (group A, 50 mg amiodarone/kg/day for 10 days, total dose 150 mg, n = 16) and long-term regimen (group B, 25 mg amiodarone/kg/day for 20 days, n = 16) (control group, n = 12). Serum, heart, and other tissues were collected for 10 days after drug cessation. Thyroxine (T4), triiodothyronine (T3), amiodarone, and its active metabolite desethylamiodarone (DEA) were determined in serum, and 5'-D was determined in tissues. In group A, amiodarone concentrations in the heart at the time of drug cessation were two times higher than in group B. Higher amiodarone concentrations were also found in other tissues, and DEA was immeasurable in nearly all tissues at all times. In all tissues the amiodarone content declined rapidly. 5'-D was depressed to about 50% of controls (p less than 0.05) in heart throughout the 10-day observation period, despite unmeasureable drug levels (less than 0.03 microgram/g tissue). In contrast, liver and kidney 5'-D normalized after the first day in both treated groups, while muscle 5'-D did not differ from controls at any time. In conclusion, heart 5'-D seems to be more sensitively depressed by amiodarone than other tissues. Inhibition of thyroid hormone effect in the heart may contribute to the antiarrhythmic properties of amiodarone; however, it cannot be concluded that amiodarone is responsible for the tardive drug effect.

Amiodarone↗
PubMed1989

Calcium stimulates the release of calcitonin gene-related peptide from the canine thyroid.

The calcitonin gene in the thyroid parafollicular cells generates two different mRNAs, which encode for the precursors of calcitonin and calcitonin gene-related peptide (CGRP). In this study, we investigated whether these two peptides are released simultaneously in the perfused dog thyroid. The isolated dog thyroid (n = 10) was once-through perfused with a Krebs-Ringer bicarbonate buffer. After elevation of the buffer Ca2+ concentration from 1.5 to 2.5 mM, a rapid, marked, and parallel secretion of both calcitonin and CGRP occurred (P less than 0.001). By stepwise increase of the buffer Ca2+ concentration, it was found that, although an elevation from 1.5 to 1.65 mM had no influence on the thyroid output of calcitonin or CGRP, elevations to 1.75, 2.0, and 2.5 mM of Ca2+ induced dose-dependent parallel increases in the thyroid output of calcitonin and CGRP. Furthermore, the stimulation with pentagastrin (100 pM) increased the thyroid output of both calcitonin and CGRP in parallel. It is concluded that the normal dog thyroid releases calcitonin and CGRP in parallel on stimulation with Ca2+ and pentagastrin.

Animals↗
PubMed1989

Thyroid hormone antibodies and Hashimoto's thyroiditis in mongrel dogs.

Abnormally elevated serum T3 concentrations measured by RIA were observed in 19 clinically euthyroid or hypothyroid mongrel dogs. The serum T4 concentrations in these sera were low, normal, or high. Measurement of the intensity of thyroid hormone binding to serum proteins was determined by equilibrium dialysis. A marked decrease in the percent free T3 was observed in these abnormal sera. Polyacrylamide gel electrophoresis, pH 7.4, of normal dog serum enriched with tracer 125I-labeled thyroid hormones demonstrated binding of [125I]T4 to transthyretin, thyroid hormone-binding globulin, and albumin and of [125I]T3 primarily to thyroid hormone-binding globulin. In all abnormal sera, polyacrylamide gel electrophoresis demonstrated strikingly higher binding of T3 to immunoglobulin (Ig). Eleven of 16 abnormal sera had minimal to moderate binding of T4 to Ig. The percent free T4 was lower only in dogs whose sera demonstrated markedly increased binding of T4 to Ig. All abnormal sera tested had positive antithyroglobulin antibodies, consistent with the diagnosis of autoimmune lymphocytic thyroiditis. As in humans, antibodies to thyroid hormones in dogs are more common in the presence of Hashimoto's thyroiditis and should be considered when elevated serum thyroid hormone concentrations are observed in the absence of clinical thyrotoxicosis. When an antibody to only one thyroid hormone is present, a marked discrepancy in the serum concentrations of T3 and T4 will be observed.

Animals↗
PubMed1989

Effects of growth hormone therapy on thyroid function of growth hormone-deficient adults with and without concomitant thyroxine-substituted central hypothyroidism.

Administration of human GH to GH-deficient patients has yielded conflicting results concerning its impact on thyroid function, ranging from increased resting metabolic rate to induction of hypothyroidism. However, most studies have been casuistic or uncontrolled and have used pituitary-derived GH of varying purity, often contaminated with TSH. Therefore, we conducted a double blind, placebo-controlled cross-over study of the effect of 4 months of biosynthetic human GH therapy (Norditropin; 2 IU/m2.day) on thyroid function in GH-deficient adults (8 females and 14 males; mean +/- SE age, 23.8 +/- 1.2 yr). One group (I) was euthyroid without T4 substitution (n = 13), whereas the other (group II) received T4 (n = 9). Serum T4 (nanomoles per L) decreased in both groups after GH treatment [group I, 100 +/- 8 (mean +/- SE) vs. 89 +/- 8 (P less than 0.01); group II, 145 +/- 18 vs. 115 +/- 10 (P less than 0.05)]. Conversely, GH treatment caused an increase in serum T3 (nanomoles per L) in both groups [group I, 1.9 +/- 0.1 vs. 2.0 +/- 0.1 (P less than 0.1); group II, 1.7 +/- 0.1 vs. 1.9 +/- 0.1 (P less than 0.05)]. Similar changes were seen in serum free T4 and T3. The serum T3 level during the placebo period of group I was significantly lower than that in an age-matched reference group (P less than 0.02). Serum rT3 (nanomoles per L) was low in group I and decreased significantly, as in group II, after GH treatment [group I, 0.26 +/- 0.02 (placebo) vs. 0.20 +/- 0.02 (GH; P less than 0.01); group II, 0.38 +/- 0.05 (placebo) vs. 0.29 +/- 0.02 (GH; P less than 0.01)]. Serum TSH decreased in both groups during GH therapy, though not significantly. Serum thyroglobulin was unaltered and did not differ from that in the reference group. In conclusion, our data are consistent with a GH-induced enhancement of peripheral deiodination of T4 to T3. GH thus seems to play an important role, either directly or indirectly, in the regulation of peripheral T4 metabolism.

Adult↗
PubMed1988

Partial purification of rat kidney iodothyronine-5'-deiodinase by zonal centrifugation.

A rapid and sensitive assay of iodothyronine-5'-monodeiodinase (5'-D) was developed using Sephadex column chromatography for separation of substrate 125I-rT3 from the product free 125I-. The distribution of 5'-D activity on rat kidney cortex cell membranes was examined in isopycnic zonal centrifugation experiments using Na,K-ATPase and NADH-cytochrome C reductase as markers for basolateral and intracellular membranes. 5'-D was mainly distributed on fractions containing endoplasmatic reticulum although some association with basolateral membranes could not be excluded. The isopycnic zonal centrifugation of a microsomal fraction prepared by differential centrifugation purified the 5'-D 8-9 times, 80-90% of membrane-bound 5'-D could be solubilized in fully active form with the detergents CHAPS and C12E8. Solubilization led to a further 2- to 3-fold purification of the enzyme. The soluble preparation was used to characterize 5'-D and as antigens in preparation of monoclonal antibodies for further purification and characterization of 5'-D.

Animals↗
PubMed1988

The adenylate cyclase system and calcitonin secretion from perfused dog thyroid lobes.

The aim of the study was to assess the involvement of the adenylate cyclase system in calcitonin (CT) secretion from thyroidal C-cells. The cAMP analogues Br-cAMP (10(-6) and 10(-4) mol/l) and DB-cAMP (10(-4) mol/l) and the activators of adenylate cyclase cholera toxin (0.1 microgram/ml and 5 micrograms/ml) and forskolin (10(-7) mol/l and 10(-5) mol/l) were infused for 6 min periods in perfused dog thyroid lobes. CT was measured in thyroid effluent by radioimmunoassay. Br-cAMP and cholera toxin did not alter basal CT secretion. DB-cAMP had a minimal stimulatory effect and forskolin 10(-5) mol/l a moderate stimulatory effect. This was much less than the effect of increasing perfusate Ca++ from 1.5 to 2.0 mmol/l. 10(-4) mol/l Br-cAMP increased the response to Ca++ with approximately 50 per cent. These results suggest that the activity of the adenylate cyclase system of the C-cells by itself is of little importance for CT secretion, but that it may have a role as modulator of the response to Ca++.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1988

Short pulses of low dose thyrotropin-releasing hormone do not affect thyroid hormone secretion from perfused dog thyroid lobes.

Small amounts of TRH are present in the thyroid, and TRH has been shown in several studies to have a moderate direct inhibitory effect on TSH-stimulated thyroid hormone secretion. In a recent publication, however, data were presented to demonstrate that very low doses of TRH given in short pulses induce immediate increases in T4 secretion from the thyroid. This type of secretion had never been observed previously. We have tried to reproduce these results employing perfused dog thyroid lobes in which small and rapid variations in the release of hormones from the follicular cells are easily detected. TRH was infused in concentrations ranging from 1.7 X 10(-11) to 1.7 X 10(-8) M for 10-min periods. There was no effect on thyroid secretion of T4 and T3, nor did the infusion of 1.7 X 10(-9) M TRH for 160 min alter the T4 secretion induced by 4 microU/ml TSH.

Animals↗
PubMed1988

Solid-phase iodothyronine-5'-deiodinase (5'-D) assays applied in production of monoclonal antibodies against 5'-D.

Characterization of iodothyronine-deiodinating enzymes has been difficult due to loss of enzyme activity during purification. To obtain a new tool for studying these enzymes we investigated the possibility of developing monoclonal antibodies (MAbs) against iodothyronine-5'-deiodinase (5'-D). Two specific and sensitive solid-phase microassays were developed for screening hybridoma supernatants for the presence of antibodies inhibiting rat kidney 5'-D and antibodies binding to but not inhibiting the enzyme. BALB/c mice were immunized with a 3-((3-cholamidopropyl)-dimethylammonio)-1-propanesulphonate (CHAPS)-solubilized 5'-D-rich membrane preparation from rat kidney cortical tissue. Spleen cells were fused with NSI-Ag 4/l mouse myeloma cells by means of polyethylene glycol. Two hybridoma cell lines (AF5 and BE8) secreting MAbs specifically binding to without inhibiting 5'-D were produced. The AF5 antibody was of the IgG2a subclass and the BE8 antibody of the IgG2b subclass. Binding of one of the antibodies to the enzyme inhibited binding of the other in both an enzyme-linked immunosorbent assay (ELISA) and a specific enzyme-binding assay. CHAPS-solubilized kidney microsomal fraction was chromatographed on a Sepharose 6B column. Elution profiles of 5'-D activity and MAb-binding antigens, as measured by ELISA with both AF5 and BE8, were identical. Monoclonal antibodies should be valuable probes in the further elucidation of the nature of the iodothyronine-deiodinating activity in various tissues.

Animals↗
PubMed1988

Urinary iodine excretion is low and serum thyroglobulin high in pregnant women in parts of Denmark.

In the Randers area of Denmark urinary iodine excretion (which reflects iodine intake) was found to be much lower than recommended intake levels, both in women in late pregnancy [52(23-118) micrograms iodine/g creatinine, median, range, n = 20] and in non-pregnant controls [42(23-71), n = 20]. Serum thyroglobulin which is high in iodine deficiency was 32.5 micrograms/l (median) (range 10.5-78.0) in the control women and considerably higher in the pregnant women [67.0 micrograms/l (9.0-385)]. This increase was probably due to the extra iodine requirement of pregnancy which was not satisfied with an adequate increase in iodine intake. The results may suggest that pregnant women in this area should receive iodine supplementation and that a general program of iodine supplementation should be considered.

Adult↗
PubMed1988

Sensitive assay for thyroglobulin autoantibodies in serum employing polyethylene glycol for precipitation.

A sensitive assay for thyroglobulin autoantibodies (Tg-ab) is described. The assay is based on prolonged incubation of [125I]Tg with serum followed by precipitation of antibody bound [125I]Tg by polyethylene glycol (PEG). The PEG concentration was chosen to give a low precipitation of free [125I]Tg while effectively precipitating Tg-ab-bound [125I]Tg. The lowest reference employed contained 19.5 MRC U/l Tg-ab. This was always different from an incubate without Tg-ab. Tg standard added to samples interfered in the assay giving spuriously low Tg-ab values as in other Tg-ab assays. Tg-ab added to samples was recovered quantitatively. The interassay coefficient of variation was 19.8% and the intra-assay coefficient of variation 11.3%. Only eight of 66 serum samples with various amounts of Tg-ab, measured with the new assay, had levels of Tg-ab detectable by the passive haemagglutination test.

Autoantibodies↗
PubMed1988

Amiodarone inhibits T4 and T3 secretion but does not affect T4 deiodination to T3 in perfused dog thyroid lobes.

Amiodarone interferes with thyroid hormone homeostasis in several ways. In the present study we assessed if amiodarone has direct effects on thyroid secretion of T4 and T3 and on intrathyroid T4 deiodination to T3 as studied in perfused dog thyroid lobes. 10(-4) mol/l amiodarone inhibited the TSH stimulated T4 secretion to 73.0 +/- 8.3 per cent of control (mean +/- SE, n = 4, p less than 0.05) and T3 secretion to 68.3 +/- 6.2 per cent of control (p less than 0.05). Amiodarone did not alter intrathyroidal T4 deiodination to T3 since the T4/T3 ratio in thyroid effluent was not affected. The mechanism behind the amiodarone effect on the thyroid is unknown but probably different from that responsible for the effect of certain other iodine containing aromatic compounds (e.g. ipodate).

Amiodarone↗
PubMed1987

Axonal transport of slow component a in sciatic nerves of hypo- and hyperthyroid rats.

Axonal transport of slow component a was studied in dorsal root afferents of the sciatic nerves of hypo- and hyperthyroid rats. Three experimental groups of rats were made hypothyroid at the age of 12 weeks by the administration of 131I. From the age of 22 weeks to the end of the study, the groups were treated with daily subcutaneous injections of thyroxine in various doses to make them hypo-(0 microgram/100 g), normo- (1 microgram/100 g), and hyperthyroid (6 micrograms/100 g), respectively. The hypothyroid group had a moderate thyroid hormone deficiency (a serum triiodothyronine level of 0.19 +/- 0.10 nmol/L and a heart/body weight ratio of 1.87 +/- 0.09 g/kg at time of killing compared with 0.60 +/- 0.09 nmol/L and 2.18 +/- 0.06 g/kg, respectively, for the control group). The hyperthyroid group was severely deranged, with serum triiodothyronine being 3.30 +/- 0.37 nmol/L and a heart/body weight ratio of 3.11 +/- 0.16 g/kg. The hypothyroid rats showed a reduction in mean velocity for the transport of slow component a (0.80 +/- 0.07 mm/day compared with 0.91 +/- 0.05 mm/day in the controls). The width of the wave of activity was smaller for the hyperthyroid group than for the control group (6.6 +/- 0.7 mm compared with 8.1 +/- 1.2 mm), suggesting an increased clearance of the axonally transported activity in the proximal axon. A decrease in transport of slow component a in hypothyroidism may be the explanation of peripheral neuropathy with axonal degeneration occasionally seen in patients with severe myxoedema.

Animals↗