• Journal of Interdisciplinary Genomics
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• v.5 no.2
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• pp.32-34
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• 2023

Resistance to thyroid hormone syndrome (RTH) is a genetic disease caused by the mutation of either the thyroid hormone receptor-β (THRB) gene or the thyroid hormone receptor-α (THRA) gene. RTH caused by THRB mutations (RTH-β) is characterized by the target tissue's response to thyroid hormone, high levels of triiodothyronine and/or thyroxine, and inappropriate secretion of thyroid-stimulating hormone (TSH). THRA mutation is characterized by hypothyroidism that affects gastrointestinal, neurological, skeletal, and myocardial functions. Most patients do not require treatment, and some patients may benefit from medication therapy. These syndromes are characterized by decreased tissue sensitivity to thyroid hormones, generating various clinical manifestations. Thus, clinical changes of resistance to thyroid hormones must be recognized and differentiated, and an approach to the practice of personalized medicine through an interdisciplinary approach is needed.

• Korean Journal of Animal Reproduction
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• v.27 no.1
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• pp.1-7
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• 2003

Transgenic rabbits were produced by DNA microinjection using growth hormone receptor (GHR) and IGF-1 receptor (IGF-1R) genes fused to metallothionein(MT) promoter. The overall efficiencies for production of transgenic rabbits were 3.2% and 3.1% for GHR and IGF-lR genes, respectively. Founder rabbits transmitted transgenes to their progenies through medelian fashion. Growth rate of GHR and IGF-lR transgenic rabbits was significantly faster than that of non-transgenic rabbits. Transgenic rabbits grew large. (25% and 15% increase in body weight of GHR and IGF-lR transgenic rabbits, respectively) than non-transgenic rabbits and organ weight of transgenic rabbits increased, suggesting that GHR and IGF-1R genes affects growth rates in transgenic rabbits.

• Asian-Australasian Journal of Animal Sciences
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• v.14 no.12
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• pp.1785-1793
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• 2001

The interaction of growth hormone with it's receptor results in dimerization of receptor, a feature known in action of certain cytokines. The interaction results in generation of number of signalling molecules. The involvement of Janus kinases, mitogen activated kinases, signal transduction and activator of transcription proteins, insulin like substrate, phosphatidylinositol 3-kinase, phospholipase C, protein kinase C is almost established in growth hormone action. There are still many missing links in explaining diversified activities of growth hormone. Amino acid sequence data for growth hormones and growth hormone receptors from a number of species have proved useful in understanding species specific effects of growth hormone. Complete understanding of growth hormone action can have implications in designing drugs for obtaining desired effects of growth hormone.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.4
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• pp.499-504
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• 2018

Objective: Recent studies have challenged the traditional paradigm that growth hormone receptor (GHR) displays physiological functions only in the cell membrane. It has been demonstrated that GHR localizes to the cell nucleus and still exhibits important physiological roles. The phenomenon of nuclear localization of growth hormone (GH)-induced GHR has previously been described in vitro. However, until recently, whether GH could induce nuclear localization of GHR in vivo was unclear. Methods: In the present study, we used pig as an animal model, and porcine growth hormone (pGH) or saline was injected into the inferior vena cava. We subsequently observed the localization of porcine growth hormone receptor (pGHR) using multiple techniques, including, immunoprecipitation and Western-blotting, indirect immunofluorescence assay and electronmicroscopy. Results: The results showed that pGH could induce nuclear localization of pGHR. Taken together, the results of the present study provided the first demonstration that pGHR was translocated to cell nuclei under pGH stimulation in vivo. Conclusion: Nuclear localization of pGHR induced by the in vivo pGH treatment suggests new functions and/or novel roles of nuclear pGHR, which deserve further study.

• Animal cells and systems
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• v.2 no.4
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• pp.489-493
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• 1998

Various heterodimers of the thyroid hormone receptor (TR) with other nuclear hormone receptors confer a wide range of transcriptional activities on thyroid hormone response elements (TREs) in the presence of the thyroid hormone ($T_3$). The present study analyzed the potential roles of retinoid X receptor (RXR) isoforms $\alpha$ and $\beta$ in $T_3$-mediated transcription on a well characterized TRE, a direct repeat of AGGTCA separated by four nucleo-tides (DR4), using electrophoretic mobility shift assays and transient transfection in CV-1 cells. We demonstrated that RXR$\alpha$ supressed liganded $TR_{\alpha}$-induced transcription while $RXR_{\beta}$ did not although both $TR_{\alpha}/RXR_{\alpha}$ and $TR_{\alpha}/RXR_{\beta}$ heterodimers were the predominant forms bound to the TRE-DR4 in the presence of $T_3$. We further demonstrated using Scatchard analysis that the two heterodimers had similar affinities for the TRE-DR4. All these observations suggest that the TRE-DR4 accomodates different types of TR/RXR heterodimers for a more finely tuned transcriptional response to $T_3$.

• Journal of Ginseng Research
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• v.27 no.3
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• pp.93-97
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• 2003

Alternative or complementary medicine plays an important role in health care system. Ginseng, being one of the most popular oriental herbs, is believed to contain various steroid hormone activity. Ginseng has been demonstrated pharmacological effect in the cardiovascular, endocrine, central nervous, and immune system. Our objective was to study that total saponin might mediate some of their actions by binding to the steroid hormone receptor, as they share many of the actions of steroid hormone in various physiological system. Using total saponin from Panax Ginseng, we have studied the possibility of total saponin being a potential estrogen receptor, androgen receptor, and retinoic acid receptor ligand. Total saponin activated the transcription of both the estrogen and androgen responsive luciferase reporter plasmids at a concentration of 100$\mu\textrm{g}$/ml in COS cells transiently transfected with the corresponding receptor and hormone responsive receptor plasmids. And total saponin caused a concentration-dependent stimulation of estrogen receptor. Total saponin increased the expression of estrogen responsive c-fos proto-oncogene at the protein level in MCF7 cells at 24 h treatment as examined by Western analysis. The c-fos induction was used as a specific marker of estrogen responsiveness. This activation was inhibited by the specific estrogen receptor antagonist, ICI 182,780. However, total saponin failed to activate the retinoic acid receptor in COS cells transiently transfected with the corresponding receptor and retinoic acid responsive reporter plasmids. These results show that total saponin is capable of activating estrogen and androgen receptors.

• Biomolecules & Therapeutics
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• v.18 no.2
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• pp.152-158
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• 2010

Melanin concentrating hormone is a neuropeptide highly expressed in the brain that regulates several physiological functions mediated by receptors in the G-protein coupled receptor family, especially plays an important role in the complex regulation of energy balance and body weight mediated by the melanin concentrating hormone receptor subtype 1 (MCH1). Compelling pharmacological evidence implicating MCH1 signaling in the regulation of food intake and energy expenditure has generated a great deal of interest by pharmaceutical companies as MCH1 antagonists may have potential therapeutic benefit in the treatment of obesity and metabolic syndrome. Although fluorescence-based calcium mobilization assay platform has been one of the most widely accepted tools for receptor research and drug discovery, fluorescence interference and shallow assay window limit their application in high throughput screening and have led to a growing interest in alternative, luminescence-based technologies. Herein, a luminescence-based functional assay system for the MCH1 receptor was developed and validated with the mitochondrial targeted aequorin. Aequorin based functional assay system for MCH1 presented excellent Z' factor (0.8983) and high signal-to-noise ratio (141.9). The nonpeptide MCH1 receptor antagonist, SNAP 7941 and GSK 803430, exhibited $IC_{50}$ values of 0.62 ${\pm}$ 0.11 and 12.29 ${\pm}$ 2.31 nM with excellent correlation coefficient. These results suggest that the aequorin based assay system for MCH1 is a strong alternative to the traditional GPCR related tools such as radioligand binding experiments and fluorescence functional determinations for the compound screening and receptor research.

• Clinical and Experimental Pediatrics
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• v.50 no.6
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• pp.576-579
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• 2007

The syndrome of resistance to thyroid hormone (RTH) is characterized by reduced tissue sensitivity to thyroid hormone (TH). In the majority of subjects, RTH is caused by mutations in the thyroid hormone receptor beta ($TR{\beta}$) gene, located on the chromosome locus 3p24.3. RTH is inherited in an autosomal dominant manner. The clinical presentation of RTH is variable, but common features include elevated serum levels of thyroid hormone (TH), a normal or slightly increased thyrotropin (thyroid stimulating hormone, TSH) level that responds to thyrotropin releasing hormone (TRH), and goiter. We report a 4 year-old girl, who was clinically euthyroid in spite of high total and free $T_4$, and $T_3$ concentrations, while TSH was slightly increased. Sequence analysis of the thyroid hormone receptor beta gene (THRB) confirmed a heterozygous C to T change at nucleotide number 1303, resulting in a substitution of histidine by tyrosine at codon 435 (H435Y). Further analysis of her parents revealed that the H435Y variation was a de novo mutation since neither parents had the variation. Her parents' TH and TSH levels were within normal range.

• Proceedings of the KSAR Conference
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• 2002.06a
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• pp.95-95
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• 2002

Transgenic rabbits were produced by micoinjection of DNA containing metallothionein promoter ligated to growth hormone receptor (GHR) and IGF-l receptor (IGF-lR) genes. Founder transgenic rabbits transmitted transgenes into pups with Medelian ratio. The mRNA expression of transgenes using Northern blotting with probes of IGF-IR and GHR genes was checked in liver of transgenic rabbits. Transgenic rabbits with IGF-IR and GHR genes more expressed mRNA than control non-transgneic rabbits. (omitted)

• Journal of Integrative Natural Science
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• v.11 no.2
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• pp.101-106
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• 2018

Corticotropin - releasing hormone receptor 1 (CRHR1) forms an integral part of the pathophysiology of disorders like post-traumatic stress disorder, stress, anxiety, addiction, and depression. Hence it is essential to look for new, potent and structure-specific inhibitors of CRHR1. We have analysed the protein-protein interaction complexes of the CRHR1 receptor with its native ligand CRF and full agonist Sauvagine. The structure of Sauvagine was predicted using homology modelling. We have identified that the residues TYR253, ASP254, GLU256, GLY265, ARG1014 and LY1060 are important in the formation of protein-protein complex formation. Future studies on these residues could throw light on the crucial structural features required for the formation of CRHR1-inhibitor complex and in studies that try to solve the structural complexities of CRHR1.