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 previously shown that highly purified urinary hCG has the potential to both stimulate the intracellular accumulation of cyclic AMP and induce growth of immortalized rat thyroid cells. We have now compared the ability of recombinant human TSH and purified urinary hCG preparations to stimulate Chinese hamster ovary (CHO) cells which have been transfected with the human TSH receptor. Only transfected CHO cells expressing recombinant TSH receptors, but not control CHO cells, were stimulated by hCG to release cyclic AMP in a dose-related manner and the effect of 100 IU of HCG was equivalent to approximately 9.2 uU of rec-hTSH. These data demonstrate that hCG interacts directly with the human TSH receptor.
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PMID:Human chorionic gonadotropin (hCG) interacts directly with recombinant human TSH receptors. 131 88

Congenital hypothyroidism was diagnosed in related Abyssinian cats. The disease appeared to be inherited as an autosomal recessive trait with affected homozygotes showing signs of reduced growth rate, shorter stature with kitten-like features, constipation and goitre. Hypothyroidism was confirmed by demonstrating low basal serum thyroxine levels which failed to increase after intravenous administration of thyroid stimulating hormone or thyrotropic releasing hormone. The radioiodide uptake of the thyroid glands was normal but a high proportion of the accumulated radioiodide was discharged after the administration of sodium perchlorate. It is concluded that the affected cats had a primary dyshormonogenesis: an organification (peroxidase) defect.
Vet Rec 1992 Aug 15
PMID:Preliminary studies on congenital hypothyroidism in a family of Abyssinian cats. 132 5

The administration of bovine TSH to stimulate thyroid radioactive iodine uptake to detect functioning thyroid tissue in man after surgery for thyroid cancer is rarely, if ever, used, due to allergic reactions and/or the development of TSH antibodies. Human (h) TSH would be far less likely to induce allergic reactions or TSH antibodies. Recombinant hTSH (rec-hTSH) was produced by a line of Chinese hamster ovary cells that had been transfected with cDNA for the two subunit proteins that comprise hTSH. The present study was carried out to determine the half-life of rec-hTSH in the monkey and its ability to stimulate thyroid function. The half-life of rec-hTSH after iv administration was approximately 63 min for the rapid phase and 326 min for the slow phase. After three daily im injections of 2 U rec-hTSH to two monkeys, serum T4 concentrations increased several-fold, and serum T3 increased 2-3 times above basal values. The 6 and 20 h thyroid 123I uptakes doubled after rec-hTSH administration. These results demonstrate the biological efficacy of rec-hTSH administered to the monkey and strongly suggest that rec-hTSH will be effective in stimulating thyroid function in man.
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PMID:Recombinant human thyrotropin stimulates thyroid function and radioactive iodine uptake in the rhesus monkey. 156 60

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

Recombinant proteins and peptides are anticipated to become promising tools as reagents for immunoassays because of their constant availability and structural uniformity. However, careful assessment of their immunological properties is necessary prior to practical use. Epitope analysis of recombinant human thyrotropin (rec-hTSH) was recently performed in our laboratory. Details are to be published elsewhere (T. Kashiwai, K. Miyai et al.) but the results are briefly shown here.
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PMID:Epitope analysis of recombinant human thyrotropin. 171 9

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

Pulsatile secretion of thyrotropin (TSH) is a well characterized phenomenon in the human, yet only limited data are available from animal studies. We propose a combined model of chronic catheterization and suppression of endogenous TSH release in the rat allowing us to apply quantified pulses of different preparations of thyrotropin intravenously with minimal interference with endogenously produced hormone. Sprague-Dawley rats treated with drinking water containing 3,5,3'-triiodothyronine (T3) showed a significant 6-fold decrease of the rat TSH (rTSH) level after four days. Free thyroxine (FT4) levels were 9-fold below unsuppressed levels; FT4 response to exogenous TSH application above this suppressed baseline level was selected as an endpoint. Infusion studies compared pulsatile with continuous TSH administration. A low and a high dose of rTSH and recombinant human TSH (rec-hTSH) were administered. Levels of FT4 were compared after two and four days and responsiveness to a standard high bolus of rTSH 6 h after end of infusion was assessed. With regard to its potency for FT4 release, differences indicating a general trend as to superior efficiency of pulsatile TSH stimulation of the thyroid gland in comparison to continuous stimulation could be observed in all four experiments. More pronounced effects were seen after 2 and 4 days of high rTSH infusion and after 4 days of low rec-hTSH infusion. Comparison of FT4 responses to rTSH boli showed a 2- and 6-fold higher response in the pulsatile group compared to the continuous group after low and high rTSH infusion, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of continuous and pulsatile administration of pituitary rat thyrotropin and recombinant human thyrotropin in a chronically cannulated rat. 775 Aug 99

Some children with juvenile hypothyroidism exhibit unexplained precocious puberty. Interaction of TSH with the human FSH receptor (hFSH-R) is a possible pathophysiological mechanism for this syndrome that has not been explored due to the lack of hFSH-free TSH preparations and the scarcity of a suitable hFSH-R-based assay system. To devise an in vitro FSH bioassay suitable for exploring this mechanism, we expressed hFSH-R complementary DNA in COS-7 cells and stimulated them with recombinant hTSH (rec-hTSH). Rec-hTSH elicited a dose-dependent cAMP response in the in vitro hFSH-R bioassay; however, the concentration of rec-hTSH required for half-maximal stimulation was several logs greater than that of hFSH. Rec-hTSH acted as a competitive inhibitor of hFSH at the hFSH-R, indicating that hTSH and hFSH are acting through the same receptor, namely the hFSH-R. This provides a potential novel mechanism for the precocious puberty of juvenile hypothyroidism.
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PMID:A potential novel mechanism for precocious puberty in juvenile hypothyroidism. 762 56

Proliferative activity of the anterior pituitary gland in 10 week-old male and female rats under normal conditions was investigated by counting mitotic figures and using single and double immunostaining of 5-bromo-2'-deoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA), and six pituitary hormones. To determine which proliferative changes depend on the estrous cycle and circadian changes, respectively, six groups of female and two groups of male rats were studied at various times of day. Additionally, BrdU-incorporated cells were further classified by the six types of hormones they contained, or as immunonegative cells. Cell proliferative activity in the females fluctuated drastically with the highest activity in estrus and the lowest in diestrus. In the males, proliferative activity was at a relatively low level, and was similar to that in females in proestrus or early estrus, with the greater activity at night. Identified by their pituitary hormones, the distribution of the proliferating cells was almost the same in each sex, with prolactin (PRL) cells accounting for the highest proportion, followed by growth hormone (GH) cells, and adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) cells. These percentages agreed well with previously reported levels of cell types among all pituitary cells of the rat. It is therefore suggested that the life span and cycle of rat pituitary cells does not differ among cell types. In another test, male and female rats were given BrdU continuously via an osmotic pump for 8 days to compare cell proliferative activity between sexes, exclusive of the influence of estrous cycle and circadian changes. In this way, we were able to demonstrate that the cumulative incorporation of BrdU in females was consistently twice as high as in males over a constant period of time, and to conclude that cell renewal occurs at a doubled rate in the pituitary of female rat.
Anat Rec 1993 Jan
PMID:Cellular proliferation in the anterior pituitary gland of normal adult rats: influences of sex, estrous cycle, and circadian change. 841 18

A quantitative analysis of the pituitary gland was conducted to ascertain the effects of protein-calorie malnutrition on the morphology of the somatotrophs, gonadotrophs, thyrotrophs, and corticotrophs. Male rats were fed a low, 8% protein diet from 20 to 50 days of age, while their age-matched controls were given a diet containing 27% protein. The hypophyses were then processed for light microscopic immunocytochemical staining using antibodies to growth hormone, the beta subunits of luteinizing hormone and thyroid stimulating hormone, and adrenal corticotrophic hormone. The number of each cell type along with an evaluation of the cell, cytoplasmic, and nuclear areas was conducted using a computerized image analyzer. All of these parameters were reduced significantly in the somatotrophs as a result of the low protein diet, while in the gonadotrophs, the cell, cytoplasmic, and nuclear areas were similarly affected. Smaller cell number, cell area, and nuclear area were noted in the corticotrophs of the malnourished animals, while in the thyrotrophs, only the cell and nuclear areas were reduced. The data demonstrate that each pituitary cell type responds in a unique manner to undernutrition.
Anat Rec 1993 Jan
PMID:Quantitative morphological analysis of the pituitary gland in protein-calorie malnourished rats. 841 20


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