Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have assessed the regulatory influence of human recombinant TSH (rec-hTSH) on its homologous receptor (TSHR) using a well characterized human fetal thyroid monolayer cell culture technique. Under the culture conditions employed, fetal human thyroid cells showed basal expression of TSHR-specific mRNA transcripts, and the addition of rec-hTSH (1 U/L) induced up to an 8-fold increase in specific mRNA over a 48-h observation period. This induction was simulated by bromo-cAMP in a dose-dependent manner, indicating that the stimulatory effect of rec-hTSH was active at the postreceptor level. Furthermore, there was no detectable increase in the transcription rate of the TSHR gene after stimulation with rec-hTSH for 12-36 h, although a marked increase in thyroglobulin-specific mRNA was observed. Rec-hTSH also had no influence on the half-life of TSHR-specific mRNA, which remained at approximately 16 h in the presence or absence of rec-hTSH. These data indicate that rec-hTSH induced up-regulation in human thyroid cell TSHR-specific mRNA and that the mechanism of this regulation was likely to be secondary to a posttranscriptional nuclear event involving changes in the regulation of primary unspliced mRNA for the TSHR.
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PMID:The positive regulation of human thyrotropin (TSH) receptor messenger ribonucleic acid by recombinant human TSH is at the intranuclear level. 157 98

We have assessed the bioactivity of newly available recombinant human TSH (rec-hTSH) using human fetal thyroid cells, with the longer term aim of assessing its use for clinical applications. Rec-hTSH caused a consistent and dose-related increase in thyroid monolayer cell cAMP release and human thyroglobulin (hTg) secretion, confirming its bioactivity. Repetitive studies (n = 5) allowed us to derive an estimated biopotency for the rec-hTSH preparation examined of 5.6 IU/mg compared to 10 IU/mg for commercially available bovine TSH for human use. The rec-hTSH had a bioimmune ratio of 0.55, similar to that of purified pituitary hTSH standards, Furthermore, rec-hTSH induced thyroid epithelial cell growth, as evidenced by a decrease in thyroid cell doubling time from 54 +/- 2.1 to 31 +/- 1.7 h (P less than 0.005). Hence, rec-hTSH is a potent glycoprotein hormone preparation when measured in a homologous human thyroid cell culture system. Rec-hTSH could serve as a future definitive International Standard and has the potential for a useful diagnostic and therapeutic reagent.
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PMID:Recombinant human thyroid-stimulating hormone: initial bioactivity assessment using human fetal thyroid cells. 185 Nov 84

The localization of immunoreactive T3 was investigated in dog and chick thyroid glands either fixed in Bouin's solution or freeze-dried and fixed with paraformaldehyde vapor, and compared with localization of 19S-thyroglobulin. Freeze-drying followed by paraformaldehyde vapor was better for the demonstration of T3 than Bouin's solution; it gave a much stronger immunoreactivity for T3. This fixative was also excellent for the demonstration of thyroglobulin. The immunoreactive T3 was detected only in the colloid and was never observed in the follicular cells, although immunoreactive thyroglobulin was present not only in the colloid but also in the follicular cells. Subsequently, in dog fetuses and chick embryos the appearance and development of immunoreactive T3 were studied. At 40 days of gestation in dog fetuses and at 9 days of egg incubation in chick embryos, immunoreactive T3 was found in the colloid of primordial follicles coinciding with the formation of the colloid. The ability of embryonic thyroid glands to synthesize T3 seems to be linked to the organization of follicles. With progressing development, the follicles stored more colloid and immunoreactive T3 within the follicular lumina. Concentrations of immunoreactive T3 in thyroids from chickens at various stages of development were also studied by radioimmunoassay. The T3 concentration was first detected at 9 days of incubation and gradually increased with embryo age; it was related to the amounts of colloid stored in the follicles.
Anat Rec 1986 Feb
PMID:Localization and development of immunoreactive triiodothyronine in thyroid glands of dogs and chickens. 395 72

Following subtotal thyroidectomy, the amount of circulating thyroid hormone decreases and causes an increase in the secretion of thyrotropin (TSH) by the anterior pituitary gland. Serum levels of circulating TSH remain elevated until thyroid secretion returns to normal. In this study we have analyzed the effects of such chronic stimulation of thyroid cells by TSH, with particular emphasis on ultrastructural and cytochemical changes in the lysosomes. Weanling Sprague-Dawley rats underwent subtotal thyroidectomy and 6 weeks later the residual thyroid tissue was removed and processed for ultrastructural and cytochemical analysis. There were obvious ultrastructural signs of hyperactivity. The cells were hypertrophied and there were colloid droplets in the cells as well as extremely abundant oddly shaped lysosomes. The lysosomes reacted positively for acid phosphatase and for glycoproteins, suggesting that they are secondary lysosomes, ones which have complexed with thyroglobulin prior to release of thyroid hormones from the cells. This tremendous increase in the number of these structures in the cells is similar to that observed under normal conditions during the aging process and suggests a slowdown in the proteolytic degradation of thyroglobulin during long periods of chronic stimulation by TSH.
Anat Rec 1986 Feb
PMID:Ultrastructure and cytochemistry of thyroid lysosomes following subtotal thyroidectomy. 395 73

In dog thyroid glands there are C cell follicles which are lined solely by C cells and which accumulate a colloidlike substance in the luminal cavities. In order to clarify the properties of the colloidlike substance secreted by C cells, the C cell follicles were stained with PAS reaction and immunoperoxidase method using anticalcitonin, anti-C-thyroglobulin, and anti-19S-thyroglobulin antisera, respectively. The colloidlike substance was PAS positive and revealed the strong immunoreaction for C-thyroglobulin but a faint reaction for calcitonin. It was nonreactive with anti-19-thyroglobulin antiserum. These results confirm that C cells synthesize the glycoprotein immunoreactive to anti-C-thyroglobulin antiserum in addition to calcitonin and can store it in the follicular lumens.
Anat Rec 1982 Sep
PMID:Immunohistochemical study of c cell follicles in dog thyroid glands. 675 11

C-cell complexes are special cell groups consisting of a mass of C-cells associated with other epithelial elements and cysts. They are remnants of ultimobranchial bodies retaining fetal characteristics. In the C-cell complexes there are follicular cells in various stages of differentiation, i.e., the cell clusters not yet organized into follicles, primordial follicles with small lumens and comparatively enlarged follicles storing plentiful amounts of colloid. They have a morphology similar to follicular cells of fetal thyroid glands and react to antiserum to 19S thyroglobulin. In order to determine whether or not the follicles in these complexes have the ability to incorporate radioiodine, autoradiography after a single injection of 125I was combined with immunoperoxidase staining using specific anti-calcitonin, anti-C-thyroglobulin, and anti-19S thyroglobulin antisera. The 19S-positive cells not yet organized into follicles did not take up radioiodine. Primordial follicles showed a heavy accumulation of silver grains over their follicular lumens storing new 19S thyroglobulin as colloid. Comparatively enlarged follicles revealed a strong autoradiographic reaction and their labeling patterns were identical with those of typical thyroid follicles. These results confirm that the follicles in C-cell complexes, as well as thyroid follicles, can incorporate radioiodine and are related to thyroid hormone synthesis. That is, functional thyroid follicles can arise from the ultimobranchial bodies.
Anat Rec 1981 Aug
PMID:Uptake of radioiodine in follicles of dog C-cell complexes studied by autoradiograph and immunoperoxidase staining. 703 Jan 41

The aim of this work was to study the effect of a dose of 150 microCi 131I on the barrier properties of the thyroid epithelium in pregnant female rats. Thirty-five female Wistar rats were divided into a control and four experimental groups (each distinguished by the time of 131I injection: group I--no less then 12 days before mating; groups II, III, and IV--on 5th, 10th, and 16th days of gestation, respectively). The thyroid glands were fixed in Bouin's fluid, embedded in paraffin, and stained immunohistochemically for thyroglobulin and fibronectin. In group IV the appearance of follicles with fibronectin-positive colloid demonstrates the penetration of blood plasma into the follicular lumen. There are more fibronectin positive follicles in group III. Regardless of the nature of the follicles' contents, numerous thyrocytes with an intensive fibronectin positive reaction begin to appear in the follicles. In group II the number of fibronectin positive follicles and thyrocytes is clearly reduced, and in group I only a few remain. In group IV there is a noticeable reduction in the quantity of colloid inside the follicles and often an absence of any thyroglobulin positive reaction. There are thyrocytes in which thyroglobulin positive granules localized in the basal zone. There is thyroglobulin positive staining in the stroma and blood vessels. In group II thyroglobulin is no longer found in the stroma. Small doses of 131I provoke a serious breakdown in the thyroid epithelium's barrier properties, although these changes are of a transient nature. The central zone of the thyroid gland reacts more actively and dynamically to exposure to radioactive iodine than the peripheral zone.
Anat Rec 1998 12
PMID:Immunohistochemical study of fibronectin and thyroglobulin in the thyroid gland of female rats after exposure to radioactive iodine. 984 10

Large bound polysomes were observed by conventional electron microscopy in surface or en face views of the rough endoplasmic reticulum (RER) in two cultured cell types. Cultured thyroid follicular epithelial cells and dermal fibroblasts, both from rats, were prepared for electron microscopy. Ultrathin sections were cut in the plane of the flattened cells to maximize the incidence of RER surface views. Some observations were also made on tissue sections of rat thyroid. Most of the large, RER-bound polysomes in both cell types appeared as two parallel rows of ribosome, thus resembling the shape of long hairpins, although probably closed at both ends. The two parallel rows of ribosomes were about 14 nm apart, and the center-to-center distance between ribosomes in the strands averaged 25 nm. Most of the large bound polysomes in thyroid epithelial cells were presumably making thyroglobulin subunits (330 kDa), while a majority of those in the fibroblasts were probably making prepro-alpha chains of collagen I (150 kDa). It was not possible in this material to see complete large polysomes, because their size usually caused them to extend out of the plane of section. In addition to the hairpin polysomes, there were smaller numbers of other forms. A characteristic large spiral polysome was seen occasionally in both cell types and contained as many as 31 ribosomes. One or two dense particles were sometimes seen in the center of spiral or circular polysomes. The consistent hairpin shape of most large bound polysomes observed in this study suggests that their shape is quite stable.
Anat Rec 1999 06 01
PMID:Shape of large bound polysomes in cultured fibroblasts and thyroid epithelial cells. 1035 13

Previous studies on the rdw rat have suggested that its dwarfism is caused primarily by dysfunction of the thyroid gland. In this study, rat thyroid glands were analyzed endocrinologically and morphologically to clarify the primary cause of dwarfism in the rdw rat. The rdw rat showed lowered thyroid hormone (T4 and T3) levels but elevated TSH in serum. The rdw thyroid gland was almost proportional in size and it was not goiter in gross inspection. Our histological investigation produced three results that may lend important evidence in understanding the problem in the thyroid gland of rdw rats. First of all, secretory granules could not be detected in the follicular epithelial cells of the rdw. Secondly, thyroglobulin was found at very low levels in the follicular lumen by immunohistochemical analysis. In contrast, it could be detected in a substantial quantity inside the dilated rER and in the huge vacuoles that are formed by swelling of the rough endoplasmic reticulum (rER) at the basal side of the follicular epithelial cells. Additionally, the nucleus of the follicular epithelial cells was pressed to the luminal side by the enlarged rER. These morphological changes would indicate that the transport of thyroglobulin is stopped at or before the formation of the secretory granules and thyroglobulin is not secreted into the follicular lumen. The rdw characterization strongly supports that rdw dwarfism is induced by hypothyroidism due to some defect(s) in the thyroid gland.
Anat Rec 2000 05 01
PMID:Missing secretory granules, dilated endoplasmic reticulum, and nuclear dislocation in the thyroid gland of rdw rats with hereditary dwarfism. 1076 Jul 44

In the follow-up of differentiated thyroid carcinoma (DTC), after total thyroidectomy and Iodine-131 therapy, thyroglobulin (Tg) levels and Iodine-131 total body have particular importance. The Tg level becomes a specific and very sensitive marker of DTC recurrence: it is usually evaluated after eradication of thyroid residual tissue (by thyroidectomy and radiometabolic therapy), in presence of high level of TSH (>35 microU/ml) obtained with the suspension of therapy or after rec-TSH administration and in absence of anti-Tg antibodies. Usually, to solve diagnostic problems in patients with negative total body Iodine-131 and high levels of thyroglobulin, we consider one or more of the following investigations, on the basis of prognostic factors: radiological examinations (neck US, skeletal X-ray, CT chest and abdomen, MRI) and scintigraphy (bone scintigraphy, Tc-MIBI or Tl-201 scintigraphy, octreoscan, PET/CT). The use of PET is well known in patients in whom carcinoma metastases are strongly suspected and who are unable of concentrating Iodine-131. In order to increase the PET sensitivity, scintigraphy is performed with high TSH levels obtained through a rec-TSH injection on the 1st and 2nd day, PET/CT scan and blood withdrawal (for Tg level evaluation) on the 3rd day. Considering the hypothesis of a recurrence with lesion size below the resolution power of the diagnostic equipment (5 mm), if PET/CT results are negative, the patients are strictly followed-up and Tg is monitored every 4-6 months. An alternative hypothesis might be not to consider the negative-PET patients as sick persons, but to attribute high Tg levels to illegitimate transcription of mRNA for Tg by the non-thyroid cells or to ectopic thyroid tissue (e.g. intrathymus). Positive PET/CT patients are evaluated for a possible surgical removal of the lesions or alternative appropriate therapies.
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PMID:[Diagnostic modalities in patients affected by differentiated thyroid carcinoma with high thyroglobulin levels and total body Iodium-131 negative: PET/CT use after recTSH]. 1576 25


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