• Title/Summary/Keyword: hormone levels

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Serum Leptin Levels and Changes in Body Weight and Obesity Index in Gwacheon Elementary School Children (과천지역 초등학생의 Leptin 수준과 열량섭취, 체중 및 비만도 변화와의 관계)

  • Kim, In-Kyoung;Kang, Jae-Heon;Song, Ji-Hyun
    • Journal of Nutrition and Health
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    • v.40 no.8
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    • pp.736-744
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    • 2007
  • Leptin, as an adipocyte-derived hormone, is an important regulator of food intake and energy expenditure. In the cross-sectional study, leptin was shown to be positively related to body adiposity and metabolic disorders in adults. However, there were very few studies which reported the leptin as a predictor of weight gain over time. We examined whether serum leptin can be used as an indicator of the present and 1-year past weight status in very young children. First grade students from elementary schools in Gwacheon City were enrolled in the study since 2005. The study subjects(total 375 students; 195 boys and 180 girls) participated in the investigation of both 2005 and 2006. Physical examinations including height, weight, waist circumference were done. To examine the prevalence of obesity, obesity index was used. Serum leptin was measured, and their nutritional status was also evaluated based on 3-Day dietary records. Serum leptin levels were strongly positively related with the value of the present BMI and with the value of the BMI one year before. We found no association with leptin levels and amount of energy intake and macronutrient intake in this children population. Children were divided into three groups according to leptin tertiles. The highest leptin tertile group showed highest prevalence of obesity in year 2006 as well as in year 2005. Serum leptin levels can reflect the weight status now and as well as 1-year before. Possibly serum leptin levels can predict the weight gain of year later. Without an action against the obesity on children with high leptin level, those children would maintain the excess adiposity growth and progress into the obesity-related metabolic disorders. Further studies are needed to predict the obesity as early as possible and preventive system then after.

Serum levels of free insulin-like growth factor-I and clinical value in healthy children (한국 소아 및 청소년에서 혈중 유리 insulin-like growth factor-I 농도치와 임상적 의의)

  • Chung, Young Hee;Chung, Woo Yeong
    • Clinical and Experimental Pediatrics
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    • v.51 no.1
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    • pp.47-53
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    • 2008
  • Purpose : The serum levels of total insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 reflect endogenous growth hormone (GH) secretion in healthy children. Free form of IGF-I which is suggested to have more potent biological action than complex form of IGF-I. The aim of this study is to investigate the serum levels of free IGF-I and its clinical value in healthy children. Methods : Serum levels of total IGF-I and IGFBP-3 were determined in 494 healthy children (248 boys and 246 girls) by RIA and IRMA. Serum level of free IGF-I was determined in 206 healthy children (103 boys and 103 girls) by IRMA. Results : The free IGF-I level increased with age in both sex. The free IGF-I level increased continuously between 7 and 15 years of age in boys, but decrement was noted after 14 years of age in girls. Serum total IGF-I level also increased with age in similar pattern of that of free IGF-I. There were no significant differences of mean values of the ratio of free IGF-I/total IGF-I in relation to age in both sex. And there were significant correlations between the level of free IGF-I and total IGF-I and the ratio of total IGF-I/IGFBP-3, respectively. Conclusion : In healthy children, serum free IGF-I increased with age in both sex and high free IGF-I level may play an important role in pubertal growth spurt. Our results suggest that the increased serum free IGF-I level in puberty may reflect changes in total IGF-I rather than IGFBP-3. But free IGF-I does not have more clinical value than total IGF-I because of no significant differences of mean values of the ratio of free IGF-I/total IGF-I in relation to age.

Effects of Chromium Picolinate on Growth Performance, Carcass Characteristics and Plasma Components in Holstein Bulls (홀스타인 수소에 있어서 Chromium Picolinate의 첨가가 성장성적, 혈액성상 및 도체품질에 미치는 영향)

  • Hong, Z.S.;Jin, M.G.;Jin, R.H.;Han, S.Y.;Lee, H.G.;Lee, H.J.;Choi, Y.J.
    • Journal of Animal Science and Technology
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    • v.44 no.4
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    • pp.419-426
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    • 2002
  • We conducted two experiments to evaluate the effects of chromium picolinate(CrP) on growth performance, carcass characteristics and plasma components in Holstein bulls. In trial Ⅰ, eight finishing Holstein bulls(300${\pm}$6.99Kg) were allocated to 2 treatments(control and 0.05% CrP) with 4 replication for 10-months. In results, growth performance was not affected by CrP addition. The plasma insulin concentration in 0.05% CrP group was about 2 times higher than the control group of Holstein bulls. The levels of plasma NEFA were significantly decreased to 59.00 mEq/dl with 0.05% CrP treatment(P<0.05), but the levels of plasma glucose and PUN were not altered by 0.05% CrP treatment. The grade of carcass was not different between control and 0.05% CrP group, but back fat thickness in 0.05% CrP group was increased in 22.33% compared with control group. In trial 2, fifteen growing- finishing Holstein bulls(160${\pm}$4.63Kg) were allocated to 3 treatments(control, 0.025% CrP and 0.05% CrP) with 5 replication for 14-months. During the overall experimental period, growth performance was not affected by CrP levels. The levels of hormone and metabolites were not affected by CrP supplementa- tion. The carcass characteristics were not different between control and treatment. These results show that the CrP may have no effects for beef cattle production because of degradation of CrP conjugation in the rumen. However treatment of short term provide a possibility the effects of development for lipogenesis.

Serum Tumor Marker Levels might have Little Significance in Evaluating Neoadjuvant Treatment Response in Locally Advanced Breast Cancer

  • Wang, Yu-Jie;Huang, Xiao-Yan;Mo, Miao;Li, Jian-Wei;Jia, Xiao-Qing;Shao, Zhi-Min;Shen, Zhen-Zhou;Wu, Jiong;Liu, Guang-Yu
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4603-4608
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    • 2015
  • Background: To determine the potential value of serum tumor markers in predicting pCR (pathological complete response) during neoadjuvant chemotherapy. Materials and Methods: We retrospectively monitored the pro-, mid-, and post-neoadjuvant treatment serum tumor marker concentrations in patients with locally advanced breast cancer (stage II-III) who accepted pre-surgical chemotherapy or chemotherapy in combination with targeted therapy at Fudan University Shanghai Cancer Center between September 2011 and January 2014 and investigated the association of serum tumor marker levels with therapeutic effect. Core needle biopsy samples were assessed using immunohistochemistry (IHC) prior to neoadjuvant treatment to determine hormone receptor, human epidermal growth factor receptor 2(HER2), and proliferation index Ki67 values. In our study, therapeutic response was evaluated by pCR, defined as the disappearance of all invasive cancer cells from excised tissue (including primary lesion and axillary lymph nodes) after completion of chemotherapy. Analysis of variance of repeated measures and receiver operating characteristic (ROC) curves were employed for statistical analysis of the data. Results: A total of 348 patients were recruited in our study after excluding patients with incomplete clinical information. Of these, 106 patients were observed to have acquired pCR status after treatment completion, accounting for approximately 30.5% of study individuals. In addition, 147patients were determined to be Her-2 positive, among whom the pCR rate was 45.6% (69 patients). General linear model analysis (repeated measures analysis of variance) showed that the concentration of cancer antigen (CA) 15-3 increased after neoadjuvant chemotherapy in both pCR and non-pCR groups, and that there were significant differences between the two groups (P=0.008). The areas under the ROC curves (AUCs) of pre-, mid-, and post-treatment CA15-3 concentrations demonstrated low-level predictive value (AUC=0.594, 0.644, 0.621, respectively). No significant differences in carcinoembryonic antigen (CEA) or CA12-5 serum levels were observed between the pCR and non-pCR groups (P=0.196 and 0.693, respectively). No efficient AUC of CEA or CA12-5 concentrations were observed to predict patient response toward neoadjuvant treatment (both less than 0.7), nor were differences between the two groups observed at different time points. We then analyzed the Her-2 positive subset of our cohort. Significant differences in CEA concentrations were identified between the pCR and non-pCR groups (P=0.039), but not in CA15-3 or CA12-5 levels (p=0.092 and 0.89, respectively). None of the ROC curves showed underlying prognostic value, as the AUCs of these three markers were less than 0.7. The ROC-AUCs for the CA12-5 concentrations of inter-and post-neoadjuvant chemotherapy in the estrogen receptor negative HER2 positive subgroup were 0.735 and 0.767, respectively. However, the specificity and sensitivity values were at odds with each other which meant that improving either the sensitivity or specificity would impair the efficiency of the other. Conclusions: Serum tumor markers CA15-3, CA12-5, and CEA might have little clinical significance in predicting neoadjuvant treatment response in locally advanced breast cancer.

Analysis of cytosine adenine repeat polymorphism of the IGF-I promoter gene in children with idiopathic short stature (특발성 저신장증 환자에서 IGF-I 프로모터 cytosine-adenine repeat 유전자 다형성의 분석)

  • Moon, Jae Hoon;Chung, Woo Yeong
    • Clinical and Experimental Pediatrics
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    • v.52 no.3
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    • pp.356-363
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    • 2009
  • Purpose : A polymorphism in the IGF-I gene promoter region is known to be associated with serum IGF-I levels, birth weight, and body length, suggesting that IGF-I gene polymorphism might influence postnatal growth. The present study aimed to investigate the role of this polymorphic cytosine-adenine (CA) repeat of the IGF-I gene in children with idiopathic short stature. Methods : The study involved 131 children (72 boys and 59 girls) diagnosed with idiopathic short stature, aged 715 years. Genomic DNA was extracted from anticoagulated peripheral whole blood. The primers were designed to cover the promoter region containing the polymorphic CA repeat. Data were analyzed using GeneMapper software. The correlations between age and serum IGF-I levels were analyzed using Spearmans correlation coefficient. Results : The CA repeat sequences ranged from 15 to 22, with 19 CA repeats the most common with an allele frequency of 40.6%. Homozygous for 19 CA repeat was 13.0%, heterozygous for 19 CA repeat was 56.5%, and 19 CA non-carrier was 30.5%. The three different genotype groups showed no significant differences in height, body weight and body mass index, and serum IGF-I levels. The serum IGF-I level and age according to the IGF-I genotypes were significantly correlated in the entire group, 19 CA repeat carrier group, and the non-carrier group. The three groups also showed no significant differences in the first year responsiveness to GH treatment. Conclusion : There were no significant different correlations between 19 CA repeat polymorphism and serum IGF-I levels according to genotype. Our results suggest that the IGF-I 19 CA repeat gene polymorphism is not functional in children with idiopathic short stature.

Testicular Development and Serum Levels of Gonadal Steroids Hormone during the Annual Reproductive Cycle of the Male Koran Dark Sleeper, Odontobutis platycephala (Iwata et Jeon) (동사리, Odontobutis platycephala (Iwata et jeon) 수컷의 생식주기에 따른 정소 발달과 혈중 생식소 스테로이드의 변화)

  • 이원교;양석우
    • Journal of Aquaculture
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    • v.11 no.4
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    • pp.475-485
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    • 1998
  • To clarify annual reproductive cycle of Koran dark sleeper, odontobutis platycephala, we examined the seasonal changes of gonadosomatic index(GSI), testicular development stages and sex steroid hormones in blood from December 1995 to November 1997. Testis was podlike shape from July to October, and tadpole-like shape from November because of its expanded posterior part. GSI was 0.14~0.18 from July to September and increased to $0.43{\pm}0.04$ in October and then was not changed significantly until February. GSI was reincreased to $0.52{\pm}0.09$ from March and then was kept at similer levels until May, but fell down to $0.28{\pm}0.05$ in June. As results of histological observation, testis was divided into 3 parts(anterior, boundary, posterior) in the development progress of germ cells. In July, the testis was composed of only spermatogonia without seminiferous tubules in most fishes. In the anterior part of testis, the ferquency of spermatogenesis stage seminiferous tubules appearing in August was more than 80% from September to December. decreased gradually from January to March and drastically in April, and then disappeared in June. The frequency of spermiogenesis stage seminiferous tubules appearing in December, increased gradually from January to March and drastically to 80% in April, and reached to 90% the highest levels of the year in June. Post-spawning stage seminiferous tubules did not appear throughout the year. The frequency of spermatogonia was 100% and 65% in July and August, and less than 20% in the rest period of the year. In the boundary part, the frequency of spermatogenesis stage seminiferous tubules appearing in August increased from September and reached to 82% in November, decreased from December, adn disappeared in March. The frequency of spermiogenesis stage seminiferous tubules appearing in November was less than 18% until February, and increased to 29%~57% from March to June. The frequency of post-spawning stage seminiferous tubules appeared 12%~25% only from March to June. The frequency of spermatogonia was 100% in July, decreased to 85% in August and 10% in November, and increased gradually from December to 50% in April, and decreased again from May to June. In the posterior part, seminiferous tubules with some seminiferous tubules increased drastically 80%~85% in August and September, decreased drastically from October to November and remained below 10% until February, and disappeared after March. The frequency of spermiogenesis stage seminiferous tubules appearing in August increased sharply from October and reached to 75% in November. decreased to 15% in December and no significant changes until March, and disappeared after April. The frequency of post-spawning stage seminiferous tubules appearing very early in November increased to 82% in December and 85%~95% until June. The frequency of spermatogonia was 100% in July, decreased drastically to 15% in August, disappeared from October to Mrch, but reappeared from April and kept at less than 10% until June. The blood level of testosterone (T) increrased gradually from August was $0.61{\pm}0.09 ng/m\ell$ in November, increrased drastically to $3.99{\pm}1.22 ng/m\ell$ in December and maintained at in similar level until March, and decreased to $0.25{\pm}0.14 ng/m{\ell} ~ 0.17{\pm}0.13ng/m{\ell}$ in April and May and no significant changes until July (P<0.05). The blood level of 17, 20 -dihydroxy-4-pregnen-3-one $ng/m{\ell}$in the rest of year without significant changes(P<0.05). Taken together these results, the germ cell development of testis progressed in the order of posterior, boundary, anterior part during annual reproductive cycle in Korean dark sleeper. The testicular cycle of Korean dark sleeper was as follows. The anterior part of testis : i.e. spermatogonial proliferation period (July), early maturation period (from August to November), mid maturation period (from December to March), late maturation period (from April to May) and functional maturation period (June) were elucidated. The boundary of testis, i.e. spermatogonial proliferation period (July), early maturation period (from August to October), mid maturation period (from November to February) and the coexistence period of late maturation, functional maturation and post-spawn (from March to June) were elucidated. The posterior of testis, i.e. spermatogonial proliferation period (July), mid maturation period (from August ot September), late maturation period (October), functional maturation period (November) and post-spawn period (from December to June) were elucidated. It was showed that the changes of sex steroid hormone in blood played a important roles in the annual reproductive cycle of Korean dark sleeper.

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Effect of Cholecystokinin on Serotonin Release from Cultured Neurons of Fetal Rat Medulla Oblongata (연수 신경세포 배양에서 세로토닌 분비에 대한 Cholecystokinin의 작용)

  • Song Dong-Keun;Cho Hyun-Mi;Lee Tae-Hee;Suh Hong-Won;Kim Yung-Hi
    • The Korean Journal of Pharmacology
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    • v.31 no.1 s.57
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    • pp.11-15
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    • 1995
  • Serotonergic neurons in medulla oblongata play an important role in the endogenous descending pain inhibitory system. To illucidate the factors involved in the regulation of medullary serotonergic neurons, we studied the effects of cholecystokinin (CCK) and agents acting on various second messenger systems on 5-hydroxytryptamine (5-HT) release from cultured neurons of rat fetal (gestational age 14th day) medulla oblongata. Cultured cells maintained for 10 days in vitro were stimulated for 48 hours with CCK or other neuropeptides at 10 micromolar concentration. CCK ($10{\mu}M$) and substance P ($10{\mu}M$) significantly increased. 5-HT release. However, somatostatin, proctolin, thyrotropin releasing hormone, and interleukin-6 did not have any effects on 5-HT release. Nimodipine ($1{\mu}M$), a calcium channel blocker, almost completely, and calmidazolium ($1{\mu}M$), a calmodulin antagonist, significantly inhibited the CCK-induced 5-HT release. The total 5-HT content (intracellular 5-HT plus released 5-HT) was significantly increased by CCK. However, the intracellular 5-HT content was not significantly changed by CCK. Forskolin ($5{\mu}M$), an adenylate cyclase activiator, but not $2{\mu}M$ phorbol myristate acetate (PMA), a protein kinase C activator, significantly enhanced 5-HT release. The total 5-HT content (intracellular 5-HT plus released 5-HT) was significantly increased by forskolin. However, the intracellular 5-HT content was not significantly changed by forskolin. PMA had no effect on intracellular 5-HT levels. These results suggest that CCK regulates serotonergic neurons in the medulla oblongata by enhancing 5-HT secretion through calcium influx and caimodulin, and that cyclic AMP system but not protein kinase C system is involved in 5-HT release.

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Effects of GnRH Agonist Administered to Mouse on Apoptosis in Ovary and Production of Estradiol and Progesterone (생쥐 내로 투여된 GnRH Agonist가 난소내 세포자연사와 Estradiol 및 Progesterone 합성에 미치는 영향)

  • Hong Soonjung;Yang Hyunwon;Kim Mi-Ran;Lee Chi-Hyeong;Hwang Kyung-Joo;Kwon Hyuck-Chan;Yoon Yong-Dal
    • Development and Reproduction
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    • v.7 no.1
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    • pp.49-56
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    • 2003
  • There have been reports that administrated high-dose gonadotropin-releasing hormone-agonist(GnRH-Ag) suppresses endogenous gonadotropin production and inhibits function of ovary. In human IVF-ET program, however, GnRH-Ag is employed in large amounts during superovulation induction resulting to luteal phase defects which must be supported with progesterone. To elucidate the reason of luteal phase defects by GnRH-Ag, the aim of this study was to investigate the apoptosis changes in the ovary and the hormonal changes in the serum after GnRH-Ag and PMSG administration in adult mice in a method similar to human superovualtion induction. GnRH-Ag(10 ${\mu}$g) or saline was injected every 12h beginning 48h prior to PMSG injection until 48h at)or PMSG injection when blood sampling and ovary collection was performed. In results, the ovary weight in the GnRH-Ag only injection group was significantly lower when compared with the other two groups, PMSG only or PMSC + GnRH-Ag injection. The ratio of preantral follicles in the ovary are increased in the GnRH-Ag only group, while the ratio of antral follicles are decreased and the corpus luteum ratio is increased in the PMSG + GnRH-Ag group. The proportion of all follicles showing apoptosis in the GnRH-Ag only in.iection group was seen to be more than twice the proportion seen in the PMSC only injection group, and such increased apoptosis is decreased after addition of PMSC. The serum levels of both estradiol and progesterone were significantly lower in the CnRH-hg only group compared to those in the other two groups. When the administration of GnRH-Ag were followed by PMSG in;ection, however, estradiol concentration was completely recovered compared to the serum level of PMSG group, but not progesterone level. In conclusion the use of GnRH-Ag in human IVF-ET program may induce the apoptosis and the suppression of hormone production by ovary leading to luteal phase defects, thus adequate progesterone support seems to be necessary against them.

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Comparison between the method of the measurement 25 Vitamin D3 (25 Vitamin D3 측정에 있어서 화학발광미세입자 측정법과 화학발광면역 측정법 간의 비교 및 고찰)

  • Kim, dae-won;Lee, jung-hee;Jung, an-na;Seo, so-yoen
    • The Korean Journal of Nuclear Medicine Technology
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    • v.19 no.2
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    • pp.112-114
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    • 2015
  • Purpose Vitamin D to Anti- Rickets both steroid compounds showing activity, By acting on bone tissue secretary and the key to maintain serum Ca homeostasis. The blood level of vitamin D is the largest in D3 that the concentration of the metabolite is reflected in the holding state of vitamin D in vivo. Sunlight to change the 7-dehydrocholesterol in the skin and through the skin to D3, In the liver in combination with the D2 and D3 D4 changes. The Radioimmunoassay(RIA) method is measuring the D 3, the sensitivity can be measured also difficult trace substance to measure the normal test because it is very sensitive, but recently, a check is possible, for the Total D3 in Chemimicroparticle immunoassay(CMIA) or Chemiluminescent immunoassay(CLIA) measuring using microparticle RIA and CMIA(Architect i2000SR) / use the CLIA(DXI-800) method to compare and evaluate the correlation between the tests in the same test items. Materials and Methods Commissioned from January 2014 to March 2015 patients were enrolled in a total of 273 people. 29 out of 273 people conducted by RIA were compared with CMIA, 244 patients were compared with CLIA. Using reagents and equipment were used RIA(Diasource), CMIA(Architect i2000SR, Abbott Diagnostics) / CLIA( Unicel DXi-800, Beckman coulter). Results Correlation of the RIA and CLIA was a R2 = 0.1844 (y = 0.7303x + 3.9005), and the correlation of RIA CMIA is R2 = 0.2762 (y = 0.8862x + 4.56) respectively. (According to statistics, during the same period RIA is Deficiency 4.31%, Insufficiency 90.53%, Sufficiency 5.16%, was Excess 0%, CLIA / CMIA is Deficiency 17.02%, Insufficiency 75.91%, Sufficiency 7.03%, indicating the distribution of 0.03 % Excess) Conclusion Serum vitamin D and parathyroid hormone that show an inverse relationship, the level above which are not parathyroid hormone and vitamin D reduced the increase. The density is different for each study, at most 20 is reported to be the maximum between 30 ng / ml. In Korea it requires a proposed standard of vitamin D deficiency, reference to the WHO lack the case more than 10ng/ml, 20ng/ml and defined by the lack of, if not more than, the IOM, but looking at 12ng/ml or less to the normal to lack, at least 20ng/ml, the reference do not match the deficit under 20ng/ml, 21-29ng/ml relative lack between, was also defined as a sufficient condition for more than 30ng/ml. Although not statistically is between RIA and CLIA two ways to vitamin D levels change according to season match, when seasonally seen in summer as commonly known (April to September), winter (October to March) relative to the increase measured than it was found. Finally, the study on the correlation between the two methods have been expected to result in a consistent and apply the same view high reference value on the graph is difficult. However, there may be differences between the test equipment and methods, and could be especially the case of RIA method using an organic solvent is difficult to compare different methods and correlated view similar trend in vitamin D deficiency and quarterly aspect ratio.

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Biological Functions of N- and O-linked Oligosaccharides of Equine Chorionic Gonadotropin and Lutropin/Chorionicgonadotropin Receptor

  • Min, K. S.
    • Proceedings of the KSAR Conference
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    • 2000.10a
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    • pp.10-12
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    • 2000
  • Members of the glycoprotein family, which includes CG, LH, FSH and TSH, comprise two noncovalently linked $\alpha$- and $\beta$-subunits. Equine chorionic gonadotropin (eCG), known as PMSG, has a number of interesting and unique characteristics since it appears to be a single molecule that possesses both LH- and FSH-like activities in other species than the horse. This dual activity of eCG in heterologous species is of fundamental interest to the study of the structure-function relationships of gonadotropins and their receptors. CG and LH $\beta$ genes are different in primates. In horse, however, a single gene encodes both eCG and eLH $\beta$-subunits. The subunit mRNA levels seem to be independently regulated and their imbalance may account for differences in the quantities of $\alpha$ - and $\beta$ -subunits in the placenta and pituitary. The dual activities of eCG could be separated by removal of the N-linked oligosaccharide on the $\alpha$-subunit Asn 56 or CTP-associated O-linked oligosaccharides. The tethered-eCG was. efficiently secreted and showed similar LH-like activity to the dimeric eCG. Interestingly, the FSH-like activity of the tethered-eCG was increased markedly in comparison with the native and wild type eCG. These results also suggest that this molecular can implay particular models of FSH-like activity not LH-like activity in the eCG/indicate that the constructs of tethered molecule will be useful in the study of mutants that affect subunit association and/or secretion. A single-chain analog can also be constructed to include additional hormone-specific bioactive generating potentially efficacious compounds that have only FSH-like activity. The LH/CG receptor (LH/CGR), a membrane glycoprotein that is present on testicular Leydig cells and ovarian theca, granulosa, luteal, and interstitial cells, plays a pivotal role in the regulation of gonadal development and function in males as well as in nonpregnant and pregnant females. The LH/CGR is a member of the family of G protein-coupled receptors and its structure is predicted to consist of a large extracellular domain connected to a bundle of seven membrane-spanning a-helices. The LH/CGR phosphorylation can be induced with a phorbol ester, but not with a calcium ionophore. The truncated form of LHR also was down-regulated normally in response to hCG stimulation. In contrast, the cell lines expressing LHR-t63I or LHR-628, the two phosphorylation-negative receptor mutant, showed a delay in the early phase of hCG-induced desensitization, a complete loss of PMA-induced desensitization, and an increase in the rate of hCG-induced receptor down-regulation. These results clearly show that residues 632-653 in the C-terminal tail of the LHR are involved in PMA-induced desensitization, hCG-induced desensitization, and hCG-induced down-regulation. Recently, constitutively activating mutations of the receptor have been identified that are associated with familial male-precocious puberty. Cells expressing LHR-D556Y bind hCG with normal affinity, exhibit a 25-fold increase in basal cAMP and respond to hCG with a normal increase in cAMP accumulation. This mutation enhances the internalization of the free and agonist-occupied receptors ~2- and ~17-fold, respectively. We conclude that the state of activation of the LHR can modulate its basal and/or agonist-stimulated internalization. Since the internalization of hCG is involved in the termination of hCG actions, we suggest that the lack of responsiveness detected in cells expressing LHR-L435R is due to the fast rate of internalization of the bound hCG. This statement is supported by the finding that hCG responsiveness is restored when the cells are lysed and signal transduction is measured in a subcellular fraction (membranes) that cannot internalize the bound hormone.

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