• Title/Summary/Keyword: TRH

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Discrepancy between in vitro and in vivo Effect of $G{\alpha}_s$ Gene Mutation on the mRNA Expression of TRH Receptor

  • Park, Seung-Joon;Yang, In-Myung;Yim, Sung-Vin;Chung, Joo-Ho;Jung, Jee-Chang;Ko, Kye-Chang;Kim, Young-Seol;Choi, Young-Kil
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.1
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    • pp.101-108
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    • 1998
  • We investigated the effect of ${\alpha}-subunit$ of the stimulatory GTP-binding protein ($G{\alpha}_s$) gene mutation on the expression of the thyrotropin-releasing hormone (TRH) receptor (TRH-R) gene in GH3 cells and in growth hormone (GH)-secreting adenomas of acromegalic patients. In the presence of cyclohexicmide, forskolin and isobutylmethylxanthine, cholera toxin, and GH-releasing hormone (GHRH) decreased rat TRH-R (rTRH-R) gene expression by about 39%, 43.7%, and 46.7%, respectively. Transient expression of a vector expressing mutant-type $G{\alpha}_s$ decreased the rTRH-R gene expression by about 50% at 24 h of transfection, whereas a wild-type $G{\alpha}_s$ expression vector did not. The transcript of human TRH-R (hTRH-R) gene was detected in 6 of 8 (75%) tumors. Three of them (50%) showed the paradoxical GH response to TRH and the other three patients did not show the response. The relative expression of hTRH-R mRNA in the tumors from patients with the paradoxical response of GH to TRH did not differ from that in the tumors from patients without the paradoxical response. Direct PCR sequencing of $G{\alpha}_s$ gene disclosed a mutant allele and a normal allele only at codon 201 in 4 of 8 tumors. The paradoxical response to TRH was observed in 2 of 4 patients without the mutation, and 2 of 4 patients with the mutation. The hTRH-R gene expression of pituitaty adenomsa did not differ between the tumors without the mutation and those with mutation. The present study suggests that the expression of TRH-R gene is not likely to be a main determinant for the paradoxical response of GH to TRH, and that $G{\alpha}_s$ mutation may suppress the gene expression of TRH-R in GH-secreting adenoma. However, a certain predisposing factor(s) may play an important role in determining the expression of TRH-R.

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TRH Stimulation Tests Compared with $T_3$ Suppression Tests in Patients With Marginal Hyperthyroidism (경도(輕度) 갑상선기능항진증환자(甲狀腺機能亢進症患者)에서 TRH 자극시험(刺戟試驗)과 $T_3$ 억제시험(抑制試驗)과의 비교연구(比較硏究))

  • Choi, Sung-Jae;Koh, Chang-Soon
    • The Korean Journal of Nuclear Medicine
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    • v.14 no.1
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    • pp.17-21
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    • 1980
  • TRH stimulation tests and $T_3$ suppression tests were done in 13 patients with clinically suspected mild or early hyperthyroidism who were all conventional thyroid function tests gave results within the accepted normal range. The results were as follows 1. 6 patients with normal $T_3$ suppression test revealed normal TRH stimulation test and could be easily diagnosed as euthyroidism. 2. 7 patients with abnormal $T_3$ suppression test exhibited no TSH response to TRH stimulation test and could be easily diagnosed as hyperthyroidism. The TRH stimulation test is a single, sensitive and reliable test of thyroid function and can well replace $T_3$ suppression test in the diagnosis of marginal hyperthyroidism.

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Enzymatic Degradation and Stabilization of Thyrotropin Releasing Hormone in Various Rabbit Mucosa Extracts (점막 추출액중 치로트로핀 유리호르몬의 효소적 분해 및 안정화)

  • Chun, In-Koo;Shin, Dong-Won
    • Journal of Pharmaceutical Investigation
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    • v.27 no.2
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    • pp.99-108
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    • 1997
  • To evaluate the feasibility of mucosal delivery of thyrotropin releasing hormone (TRH) through various mucosae, enzymatic degradation and stabilization of TRH in the nasal, rectal and duodenal extracts of rabbits were studied. TRH in the extracts was assayed by HPLC and its degradation was found to follow apparent first-order kinetics. The residual concentrations of TRH in the mucosal extracts of nasal, rectal and duodenal segments after 24 hr of incubation were found to be $65.1({\pm}1.1),\;19.7({\pm}2.7)$ and 0%, and in the serosal extracts, $65.6({\pm}5.5),\;75.2({\pm}1.1)$ and $68.7({\pm}1.4)%$, respectively. This result suggests that there is a significant difference in the activity of TRH-degrading enzymes among the sites of administration. The inhibition of TRH degradation in the mucosa extracts was kinetically investigated using various additives such as thimerosal, benzalkonium chloride, disodium edetate, ${\sigma}-phenanthroline$, dithiothreitol and dithioerythritol, and $IC_{50}$ values of inhibitors were calculated. The results obtained showed that thimerosal (0.5 mM) and benzalkonium chloride (0.141 mM) protected TRH from the enzymatic degradation in all the mucosa extracts more than 95% after 24 hr of incubation.

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Process Development for Large Scale Synthesis of TRH (TRH의 대량합성 제조법 개발)

  • Kim, Dong-Hyeon;Thapa, Pritam;Karki, Radha;Jahng, Yurng-Dong;Lee, Eung-Seok
    • YAKHAK HOEJI
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    • v.51 no.6
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    • pp.490-494
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    • 2007
  • TRH (thyrotropin-releasing hormone) was chemically synthesized utilizing solution phase peptide chemistry for the process development of large scaled synthesis. All the synthetic steps performed in relatively mild conditions, higher yields, easier preparations, minimum racemizations, and separation and purification by recrystallizations.

TSH Response to the Intravenous Administation of Synthetic TRH in Various Thyroid Diseases (각종(各種) 갑상선질환(甲狀腺疾患)에서 합성(合成) TRH 정주후(靜注後) 혈중(血中) TSH 변동(變動)에 관(關)한 연구(硏究))

  • Choi, Sung-Jae;Kim, Kwang-Won;Lee, Mun-Ho
    • The Korean Journal of Nuclear Medicine
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    • v.14 no.1
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    • pp.1-8
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    • 1980
  • Serum TSH levels were measured by radioimmunoassay before and after intravenous administration of synthetic thyrotropin-releasing hormone (TRH) to 15 normal subjects and 55 patients with primary thyroid disease (14 patients with euthyroidism, 24 patients with thyrotoxicosis and 17 patients with hypothyroidism) to evaluate pituitary TSH reserve and its diagnostic availability. The observed results were as follows. 1. In normal subjects, serum TSH responses to synthetic TRH were $3.2{\pm}1.0$ at 0min (baseline TSH level), $8.0{\pm}4.0$ at 10min, $11.7{\pm}5.0$ at 20min, $13.7{\pm}7.1$ at 30min, $9.7{\pm}5.0$ at 60min., $5.2{\pm}2.0$ at 120min. and $3.6{\pm}0.4{\mu}U/ml$ at 180 min. Serum TSH peaked at $20{\sim}30$ minutes and returned nearly to baseline at 180minutes. 2. In euthyroid group, serum TSH responses to synthetic TRH were $3.3{\pm}1.6$ at 0min, $8.6{\pm}8.0$ at 10min, $10.9{\pm}8.5$ at 20min, $12.5{\pm}8.4$ at 30min, $9.0{\pm}5.9$ at 60min, $5.6{\pm}2.6$ at 120min and $3.5{\pm}1.3{\mu}U/ml$ at 180min. No significant difference revealed between euthyroid group and normal subjects (p>0.05). 3. In hyperthyroid group, serum TSH responses to synthetic TRH were $1.5{\pm}0.6$ at 0min, $2.2{\pm}0.8$ at 10min., $2.3{\pm}1.0$ at 20min., $2.4{\pm}1.5$ at 30min., $2.1{\pm}1.1$ at 60min., $1.9{\pm}0.2$ at 120min. and $1.5{\pm}0.8{\mu}U/ml$ at 180min., No response to TRH showed. 4. In hypothyroid group, mean values of serum TSH response to synthetic TRH were 42.0 at 0min., 60.6 at 10min., 124.8 at 20min., 123.0 at 30min., 101.6 at 60min., 64.3 at 120min. and $15.5{\mu}U/ml$ at 180 min., Patients with primary hypothyroidism showed an exaggerated TSH response to synthetic TRH despite their high basal TSH. 5. Side effects attending synthetic TRH administration were transient nausea (59.0%), desire to micturate (59.0%), feeling of flushing(19.7%), dizziness (45.9%), metallic taste (9.8%) and headache (19.7%). Any side effect didn't show in 16.4%. These symptoms began almost immediately after TRH intravenous injection and lasted several minutes, and not related to dose or response in the person experiencing it.

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Role of Calcium Influx in mediating the TRH-induced c-fos Gene Expression (갑상선자극 분비 호르몬에 의해 유도되는 c-fos 유전자 발현에서 Ca2+의 역할에 관한 연구)

  • Seung Kirl Ahn;Don
    • The Korean Journal of Zoology
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    • v.36 no.4
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    • pp.487-495
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    • 1993
  • TRH (Thvrotropin-Releasing Hormone) known to regulate the transcription of the TSH (Thyroid-Stimulating Hormones gene in pituitary cells, but little is understood about the mechanism(sl involved. re present study was attempted to elucidate the role of Ca2+ movement through the voltage-gated channels in the regulation of TSH gene transcription. The c-fos is one of immediate early genes and used as model system for the investigation of signaling pathwavs involved in various stimuli. The changes of c-fos mRNA levels were determined after treatment of various agents using Northern and slot hybridization analysis. The c-fos mRNA was rapidly and transiently induced by TRH (about 3-fold) in GH3 cells and this induction was repressed by calcium chelating agent (EGTA), calcium channel blocker (verapamil) anti protein kinase C inhibitor (aminoacridine). The abilities of forskolin (adenvlate cvclase activators, PMA (protein kinase C activator), and A23187 (calcium ionophore) to affect c-ios gene transcription, either alone or in combination with TRH were tested in the same cells. All of them significantly increased the level of c-fos mRUA. However, no additive relationship was observed in all combined treatments except forskolin. These results suggest that TRH action on the c-fos gene activation is mediated by calcium influx as well as through protein kinase C.

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Enhanced Transmucosal Permeation of Thyrotropin-releasing Hormone (치로트로핀 유리 호르몬의 점막 투과 증진)

  • 전인구;신동원
    • Biomolecules & Therapeutics
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    • v.7 no.3
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    • pp.263-270
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    • 1999
  • The in vitro permeation of thyrotropin-releasing hormone (TRH) through rabbit nasal, rectal and duodenal mucosae was studied in the absence and presence of an enzyme inhibitor and permeation enhancer. TRH in the donor and receptor solutions was assayed by HPLC. When thimerosal (TM, 0.5 mM) was added to the donor cell as an inhibitor, the permeation rate of TRH (200 $\mu\textrm{g}$/ml) increased linearly as a function of time. Fluxes of TRH through the nasal, rectal and duodenal mucosae were found to be 33.3$\pm$5.9, 11.8$\pm$1.9 and 9.6$\pm$0.7 $\mu\textrm{g}$/$\textrm{Cm}^2$/hr, respectively. The addition of sodium glycocholate, glycyrrhizic acid ammonium salt, sodium taurodihydrofusidate or L-$\alpha$-lysophosphatidylcholine to the donor solution containing TM did not result in the significant increase of permeation flux except for the duodenal mucosa, comparing with that in the presence of TM alone. Consequently, it was suggested that the nasal route was advantageous for systemic delivery of TRH, and the addition of TM and/or an enhancer was necessary to maximize the transmucosal permeation of TRH.

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Characterization of Thyrotrpin Releasing Hormone Receptor in Brain (뇌의 Thyrotropin Releasing Hormone 수용체 분포에 관한 연구)

  • Koong, Sung-Soo;Kim, Seung-Taik;Chung, June-Key;Lee, Myung-Chul;Cho, Bo-Youn;Koh, Chang-Soon;Yoo, Eun-Sook;Park, Eun-Mey;Seo, Il-Tak
    • The Korean Journal of Nuclear Medicine
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    • v.24 no.1
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    • pp.93-100
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    • 1990
  • To evaluate the utility of autoradiographic technique in the detection of TRH receptor changes in brain after the various kinds of stimulation or drug administration, we tried the characterization of TRH receptor in mouse brain and autoradiography in rat brain as a preliminary study. The Kd value of [3-H] MeTRH to TRH receptors of adult male ICR mouse brain (cebellum and spinal cord were excluded) was 3.55+0.6 nM and Bmax was 3.44+0.52 fmol/mg wet tissue by saturation analysis. The Kd value of TRH to TRH receptors was 133.8+28.2 nM by competition analysis. And we could visualize the distribution of TRH receptors in rat brain by autoradiographic technique.

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Suppression of Citrus Melanose on the Leaves Treated with Rhizobacterial Strains after Inoculation with Diaporthe citri (식물근권세균 처리에 의한 감귤 검은점무늬병에 대한 방제 효과)

  • Ko, Yun Jung;Kang, So Young;Jeun, Yong Chull
    • Research in Plant Disease
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    • v.18 no.4
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    • pp.331-337
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    • 2012
  • Citrus melanose is one of important disease in citrus cultivation, reducing quality of citrus fruits and resulting in economic loss. Like other diseases in citrus, melanose was mainly protected by chemical fungicide in the field. Recently, alternative method of disease control is highly required due to the side effect of the chemicals. In this study four rhizobacterial strains TRH423-3, MRL408-3, THJ609-3, and TRH415-2 are selected by dual-culture testing its antifungal activity against Diaporthe citri causing citrus melanose. To investigate the protection efficacy of the selected rhizobacterial strains to citrus melanose, the bacteria were pre-treated on citrus leaves following inoculation with melanose pathogen. Pre-treatment with all selected rhizobacterial strains showed disease suppression in which the levels of protection rates were different by the rhizobacterial strains. Additional treatment with the rhizobacterial strains after the pathogen inoculation enhanced protection rates in all cases. The strain MRL408-3 and TRH423-3 were identified as Burkholderia gladioli, TRH415-2 as Pseudomons fluorescens and THJ609-3 as Pseudomonas pudia as a result of analyzing the internal transcript spaces of the rhizobacterial strains rDNA. The selected rhizobacterial strains may be valuable as biological control agents in the environment-friendly citrus farm in which chemical application is limited.