Biomedical subjects

E G Moura

Publications and source records attributed to E G Moura.

9 recordsLinked to original sources

PubMed1992

Role of neuromedin B in control of the release of thyrotropin in hypothyroid and hyperthyroid rats.

Neuromedin B (NB) is a recently discovered neuropeptide related to bombesin. It is localized to thyrotropes and we have previously shown that it directly inhibits thyrotropin (TSH) release from the anterior pituitary gland of euthyroid rats. In the current studies, we further evaluated the action of NB and antiserum directed against it in euthyroid rats and compared the actions with those in hypo- and hyperthyroid rats. Rats were rendered hypothyroid by treatment with propylthiouracil and hyperthyroid by treatment with thyroxine. In euthyroid rats, NB suppressed TSH release from hemipituitaries in vitro. Incubation of these pituitaries with highly specific antiserum against NB produced a stimulation of TSH release, whereas normal rabbit serum had no effect on the output of TSH. Thus, in euthyroid animals NB is a physiologically significant inhibitor of TSH release from the pituitary. In hypothyroid as in euthyroid animals, NB inhibited TSH release when microinjected into the third ventricle (3V) in the same dose (0.5 micrograms; 0.44 nmol) as in euthyroid rats. TSH release from hemipituitaries of hypothyroid animals was also suppressed by NB as in euthyroid animals. In hypothyroid animals, anti-NB antiserum was ineffective both in vivo after its microinjection into the 3V and in vitro on hemipituitaries, which suggests that the peptide has little physiologic significance in this condition, presumably because of its reduced release from the thyrotropes associated with diminished NB content in the pituitary of the hypothyroid rat. Intraventricular injection of NB failed to lower plasma TSH in hyperthyroid rats, which suggests that the action of the peptide is already maximal in hyperthyroidism. When antiserum to NB was microinjected twice into the 3V, there was a delayed increase in plasma TSH manifest 24 hr after the initial injection. TSH release from pituitaries of these animals was markedly increased in the presence of NB antiserum. Thus, NB has a physiologically significant TSH release-inhibiting action at the pituitary in the hyperthyroid as well as in the euthyroid rat. We conclude that in the euthyroid animal NB acts in an autocrine fashion to suppress TSH release from the thyrotropes directly. In hypothyroidism, NB synthesis and presumably release from the pituitary is decreased, such that there is no physiologic significance to the residual NB release, although the responsiveness to the inhibitory action of the peptide is increased, possibly via upregulation of its postulated receptors on the thyrotrope. In hyperthyroidism, the concentration of NB in thyrotropes and presumably its release is increased so that it has a physiologically significant TSH release-inhibiting action.

Animals↗

PubMed1991

Effect of iodine deficiency and cold exposure on thyroxine 5'-deiodinase activity in various rat tissues.

We measured thyroxine 5'-deiodinase I (T(4)5'D-I) activity in thyroid, liver, and kidney and thyroxine 5'-deiodinase II (T(4)5'D-II) activity in brown adipose tissue (BAT) in rats on a low-iodine diet (LID) to test the possibility that increased deiodinase activity in these tissues might contribute to the maintenance of ther serum 3,5,3'-triiodothyronine (T3) level. Control rats received LID plus KI. Experiments were also performed with LID and LID plus KI rats exposed to cold. T(4)5'D-I activity was greatly increased in the thyroids of LID rats but not in liver or kidney. We consider it likely that increased thyroxine (T4)-to-T3 conversion in the greatly enlarged thyroids of LID rats contributed to the maintenance of serum T3. T(4)5'D-II activity in BAT was markedly increased in LID rats and was further greatly increased on cold exposure. However, we were unable to demonstrate an increase in uncoupling protein mRNA levels in BAT in response to cold in LID rats. We attribute this to the very low serum T4 level, which limits substrate availability. This factor also makes it unlikely that BAT contributes to maintenance of serum T3 in LID rats.

Acclimatization↗

PubMed1991

Enzymatic deglycosylation of porcine thyroid peroxidase: effects on catalytic activity and immunoreactivity.

Thyroid peroxidase is a heme-containing, membrane-bound, glycoprotein enzyme that catalyzes iodination and coupling in the thyroid gland. It is also the antigen for microsomal autoantibodies that are commonly found in the serum of patients with autoimmune thyroid disease. We examined the effect of deglycosylation on the catalytic functions and the immunoreactivity of this enzyme. A highly purified, solubilized, large tryptic fragment of porcine thyroid peroxidase, retaining all of the N-linked glycosylation sites of the native enzyme and displaying full catalytic activity was used. It was deglycosylated by treatment with N-glycanase under nondenaturing conditions. The loss in relative molecular mass after treatment, determined by gel electrophoresis, was about 75% of the estimated molecular weight of the glycan portion of porcine thyroid peroxidase. Lectin blots performed with horseradish peroxidase-conjugated concanavalin A showed a similar loss in relative molecular mass but some residual carbohydrate. The intensity of the carbohydrate stain was consistent with the loss of about 75% of the glycans. Despite this loss, three different assays for catalytic activity of porcine thyroid peroxidase were not significantly decreased. Immunoreactivity measured by immunoblotting and by enzyme-linked immunosorbent assay was also unimpaired. These findings suggest that N-glycanase-sensitive glycans in porcine thyroid peroxidase do not act as antigenic determinants and play a minor role, if any, in catalytic activity and, presumably therefore, in the maintenance of protein conformation.

Animals↗

PubMed1990

Nailfold capillaroscopy in non-insulin dependent diabetes mellitus: blood flow velocity during rest and post-occlusive reactive hyperaemia.

Direct intravital microscopic examinations of nailfold capillaries were made in two groups of subjects: 15 healthy volunteers (C) and 16 non-insulin dependent (D II) diabetic patients. In the diabetic group, the disease duration was less than 1 year (n = 4), between 1 and 10 years (n = 8) and between 10 and 18 years (n = 4). Capillary morphology was evaluated and the distribution of morphological patterns was significantly different between the two groups (P less than 0.001). The number of enlarged capillaries was increased in the D II group compared to the C group and capillaries with nodular apical elongations were only found in diabetics. Capillary blood flow velocity (CBFV) was measured during rest and after release of 60 s arterial occlusion. To assess autoregulatory capacity we determined peak CBFV post occlusion and time to reach it in single capillaries. Mean resting CBFV was not statistically different in the two groups but mean peak CBFV post occlusion was significantly lower (C: 1.49 +/- 0.14 mm s-1; mean +/- SE; D II: 0.93 +/- 0.13 mm s-1, P less than 0.05) and mean time to reach it significantly prolonged (C: 8.9 +/- 0.6 s; D II: 18.0 +/- 1.9 s; P less than 0.05) in diabetics compared to controls. Thus skin microvascular autoregulatory responses are disturbed in these patients. The impairments of the reactive hyperaemia response could not be correlated to either metabolic control or duration of the disease.

Adult↗

PubMed1990

Lack of effect of propylthiouracil and methylmercaptoimidazole on thyroglobulin biosynthesis.

Experiments were performed both in vivo and in vitro to test a previous proposal that part of the antithyroid action of the thioureylene drugs, propylthiouracil (PTU) and methylmercaptoimidazole, can be attributed to inhibition of thyroglobulin (Tg) biosynthesis. Rat thyroid lobes were incubated in leucine-free Eagle's medium containing bovine thyroid-stimulating hormone and 0, 0.1-0.2, or 1 mM drug. After a 30-min preincubation, 5 mu Ci of [14C]leucine were added and the incubation was continued for 4 hr. The soluble fraction was analyzed by sucrose density gradient centrifugation, and the fractions corresponding to the 19S Tg peak were pooled and assayed for 14C. No inhibition of 14C incorporation into 19S Tg was observed, even in thyroid lobes incubated in the presence of 1 mM methylmercaptoimidazole or 2 mM PTU. At the same time, 14C incorporation into 19S Tg was completely inhibited when lobes were incubated in the presence of 0.1 mM puromycin. In vivo, rats received an injection of PTU (1 mumol/100 g body wt), followed 60 min later by an injection of 25 mu Ci of [14C]leucine. Blood samples and thyroids were taken 5 hr after the [14C]leucine injection. Serum thyroid-stimulating hormone was not significantly affected by the PTU injection. The thyroid-soluble fraction was analyzed by sucrose density gradient centrifugation. No significant differences between saline and PTU-injected groups were observed in [14C]leucine incorporation into 19S Tg. We conclude from both our in vitro and our in vivo studies that PTU and methylmercaptoimidazole have no inhibitory effect on thyroglobulin synthesis in rat thyroids and that such inhibition does not play a significant role in the antithyroid action of these drugs.

Animals↗

PubMed1989

Thyroid peroxidase activity in human nodular goiters.

1. Thyroid peroxidase (TPO, iodide-oxidation) activity was evaluated in nodular and paranodular tissue samples from 27 patients with nodular goiter (19 "cold" and 8 "hot" nodules), and compared to 11 diffuse toxic goiter and 9 normal thyroid tissue samples. 2. In terms of U/g digitonin solubilized protein, TPO activity was increased in hot nodules (P less than 0.05), although not as much as in diffuse toxic goiters (P less than 0.01). 3. The mean TPO activity of tissues paranodular to a cold nodule was not different from that of normal thyroids. 4. Both the highest and the lowest TPO activities were found in cold nodules, but their mean value did not differ from those of their paranodular tissues or normal thyroids. 5. Inter-tissue variability was significantly increased (P less than 0.01) in cold nodules and in tissues paranodular to a hot nodule. 6. These data show that heterogeneity both within and among tissues contributes to the wide range of TPO activity detected in nodular goiters.

Adult↗

PubMed1988

Lack of correlation between peroxidase activity and iodothyronine levels in human and murine thyroid tissues.

Since thyroid peroxidase (TPO) is essential in thyroid hormone biosynthesis, we evaluated whether a correlation exists between TPO activity and iodothyronine stores in human thyroid tissues from nodular goiters with scintigraphically "cold" (N = 10) or "hot" (N = 7) nodules, diffuse toxic goiters (N = 6), and in normal rat thyroids (N = 18). T4, T3 and rT3 were significantly correlated (rs greater than 0.84, P less than 0.001) in human thyroid tissues, although no correlation between TPO activity and any of the iodothyronines was found. Both TPO and the iodothyronines in human goitrous thyroid glands showed great variation which may mask an underlying relationship. However, this is unlikely since no correlation was found between the much less variable TPO and T4 or T3 in the normal murine thyroid. Other factors related to iodothyronine synthesis and secretion must be at least as important as TPO in determining thyroidal stores.

Analysis of Variance↗

PubMed1987

Thyroid function in fasting rats: variations in 131I uptake and transient decrease in peroxidase activity.

Serum thyroxine and triiodothyronine, radioiodide thyroid uptake and thyroid peroxidase (TPO) activity were studied over a 2 to 5 day period in fasting rats treated (F+) or not (F-) with TSH. In F- rats, TPO activity was transiently decreased on the 3rd day, whereas in F+ it was always higher than in controls. On the 5th day, the 2 h thyroid uptake of 131I decreased in F-, while the 24 h uptake increased in both F- and F+. Serum T3 and T4 decreased in both fasting groups. Thus, not all effects of fasting on rat thyroid function are reverted by TSH administration, suggesting intrinsic impairment of glandular function.

Animals↗

PubMed1987

Nailfold capillaroscopy in diabetes mellitus: morphological abnormalities and relationship with microangiopathy.

The morphology and density of nailfold capillaries were evaluated in patients with Type I and Type II diabetes mellitus and in healthy controls, using videocapillaroscopy. A protocol of well-defined capillary patterns was used. Diabetic patients had more tortuous and enlarged capillaries than controls. Nodular apical elongation was found only in diabetics and was more frequent in patients with a longer history of disease. Type II diabetic patients with chronic clinical complications had a higher frequency of enlarged capillaries and nodular apical elongation. Glycemic control was without influence. Capillary density did not differ among the groups.

Capillaries↗