Objectives : The aim was to investigate the characteristics of low dose effect and non monotonic dose responses(NMDRs) and to predict the influence it might have on the health and medicine, traditional Korean medicine. Methods : By investigating recently published major literatures related to low dose effect and NMDRs, the definition, mechanism, major related fields, and the influence on public health and medicine has been categorized and summarized. Results : Although there are still heated debates about the definition of low dose, it implies the biological responses in environmental exposure level and the NDMDRs means the nonlinear relationship between the dose-response in the slope sign change. Also, it implies the new form of the curve showing a U, reverse U shape, and the slop sign constantly changing showing various forms. This mechanism is because the two acceptor shows opposing effects to toxic materials and the affinity is different along with the numerical value that increase and decrease being different. These characteristics generally appear in endocrine disrupters such as bisphenol A, agricultural pesticides, metal, and radiation. The research field in the public health and medical treatment is obesity, problems in metabolism, growth hormone treatment, climacteric treatment, breast cancer, intake of Korean traditional medicine for pregnancy, menopause and phytoestrogen. Conclusions : As a result of discussing implications, NMDRs is a particular effect in low dose and heated debates surround this response, research is being conducted surrounding the field of obesity, problems in metabolism, growth hormone treatment, climacteric treatment, breast cancer, intake of Korean traditional medicine for pregnancy, menopause, and phytoestrogen. More research and interest in needed as it can have a massive influence in the public health and medicine.
In 27 patients with the past history of poor response to the gonadotropin superovulation induction due to poor follicular growth or permature surge of endogenous luteinizing hormone, the effectiveness of pituitary supperssion with the gonadotropin releasing hormone agonist(GnRH-a) in in vitro fertilization(IVF) program was evaluated in 43 cycles using a combination regimen of D-Trp-6 LHRH(Decapeptyl, Ferring)and FSH/hMG from June, 1989 to August, 1990 at Korea University Hospital IVF Clinic. At midluteal phase of menstrual cycle, Decapeptyl-CR was administered by long-term protocol to minimize initial agonistic effect of endogenous gonadotropins. After the confirmation of pituitary suppression, about 2-3 weeks after GNRH-a administration, ovarian follicle growth was stimulated with FSH/hMG and followed by transvaginal ultrasonic measurement of follicle size and by monitoring of serm E2 and LH if necessary. When compared with the control group stimulated with gonadotropin regimen only, the cancellation rate and occurrence rate of premature LH surge during gonadotropin treatment were significantly lower in study group(11.6% and 2.4%, respectively). There is no significant differences in the mean number of aspirated oocytes, fertilization/cleavage rate, embryo transfer(ET) rate, and mean number of embryos transferred between the two groups. The pregnancy rate per treatment cycle, 16.3%, and per ET cycle, 23.3%, were significantly higher in the study group compared with those of control group. These data suggest that GnRH-a therapy is effective for previous poor responder In gonadotropin superovulation induction for IVF.
Objective: Follicle-stimulating hormone (FSH) is the central hormone involved in mammalian reproduction, maturation at puberty, and gamete production that mediates its function by control of follicle growth and function. The present study investigated the mutations involved in the regulation of FSH receptor (FSHR) activation. Methods: We analyzed seven naturally-occurring mutations that were previously reported in human FSHR (hFSHR), in the context of equine FSHR (eFSHR); these include one constitutively activation variant, one allelic variant, and five inactivating variants. These mutations were introduced into wild-type eFSHR (eFSHR-wt) sequence to generate mutants that were designated as eFSHR-D566G, -A306T, -A189V, -N191I, -R572C, -A574V, and -R633H. Mutants were transfected into PathHunter EA-parental CHO-K1 cells expressing β-arrestin. The biological function of mutants was analyzed by quantitating cAMP accumulation in cells incubated with increasing concentrations of FSH. Results: Cells expressing eFSHR-D566G exhibited an 8.6-fold increase in basal cAMP response, as compared to that in eFSHR-wt. The allelic variation mutant eFSHR-A306T was not found to affect the basal cAMP response or half maximal effective concentration (EC50) levels. On the other hand, eFSHR-D566G and eFSHR-A306T displayed a 1.5- and 1.4-fold increase in the maximal response, respectively. Signal transduction was found to be completely impaired in case of the inactivating mutants eFSHR-A189V, -R572C, and -A574V. When compared with eFSHR-wt, eFSHR-N191I displayed a 5.4-fold decrease in the EC50 levels (3,910 ng/mL) and a 2.3-fold decrease in the maximal response. In contrast, cells expressing eFSHR-R633H displayed in a similar manner to that of the cells expressing the eFSHR-wt on signal transduction and maximal response. Conclusion: The activating mutant eFSHR-D566G greatly enhanced the signal transduction in response to FSH, in the absence of agonist treatment. We suggest that the state of activation of the eFSHR can modulate its basal cAMP accumulation.
The purpose of this study was to determine the effect of energy supplement on responses of plasma insulin-like growth factor (IGF)-1 and IGF binding proteins (IGFBPs) to growth hormone-releasing peptide-2 (GHRP-2) administration in normal protein-fed wethers, and to observe the effect of GHRP-2 treatment on hepatic growth hormone (GH) receptor in well-fed wethers. Plasma IGF-1 and 39-42 kDa IGFBP-3 during the HENP (CP, crude protein 0.34 and TDN, total digestible nutrients 1.83 kg/day DM, dry matter intake) treatment period were higher than in the LENP (CP 0.32 kg and TDN 0.87 kg/day DM intake) period (P<0.05). The response of GH was stimulated by GHRP-2 ($12.5\;{\mu}g/kg$ body weight/day) administration during both of the feed treatment periods (P<0.05). The area under curve (AUC) increment and average concentration of GH (0-180 min) with GHRP-2 administration was higher during HENP treatment than LENP treatment (P<0.01). During the HENP treatment period from day 1 to day 7 of twice daily GHRP-2 treatment, the plasma IGF-1 increment was increased on days 2, 6 and 7 of GHRP-2 administration (P<0.05). On the basis of ligand blotting, the proportions of plasma 39-43 kDa IGFBP-3 during the HENP treatment period only showed a significant difference on days 6 and 7 with GHRP-2 administration. No significant difference in the specific binding of $^{125}I-labeled$ oGH to hepatic membranes was detected between the saline and GHRP-2 treatments of the HENP-fed wethers. These results suggest that the nutritional balance between energy and protein may affect the endogenous GH / IGF-1 axis as well as plasma IGFBP-3 levels.
The misuse of anabolic hormones or illegal drugs is a ubiquitous problem in animal husbandry and in food safety. The ban on growth promotants in food producing animals in the European Union is well controlled. However, application regimens that are difficult to detect persist, including newly designed anabolic drugs and complex hormone cocktails. Therefore identification of molecular endogenous biomarkers which are based on the physiological response after the illicit treatment has become a focus of detection methods. The analysis of the 'transcriptome' has been shown to have promise to discover the misuse of anabolic drugs, by indirect detection of their pharmacological action in organs or selected tissues. Various studies have measured gene expression changes after illegal drug or hormone application. So-called transcriptomic biomarkers were quantified at the mRNA and/or microRNA level by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) technology or by more modern 'omics' and high throughput technologies including RNA-sequencing (RNA-Seq). With the addition of advanced bioinformatical approaches such as hierarchical clustering analysis or dynamic principal components analysis, a valid 'biomarker signature' can be established to discriminate between treated and untreated individuals. It has been shown in numerous animal and cell culture studies, that identification of treated animals is possible via our transcriptional biomarker approach. The high throughput sequencing approach is also capable of discovering new biomarker candidates and, in combination with quantitative RT-qPCR, validation and confirmation of biomarkers has been possible. These results from animal production and food safety studies demonstrate that analysis of the transcriptome has high potential as a new screening method using transcriptional 'biomarker signatures' based on the physiological response triggered by illegal substances.
A trial was conducted to investigate the effect of dietary NMA on several growth associated hormones and fat metabolism in finishing pigs. A total of 84 crossbred finishing pigs (average initial BW of $56{\pm}$0.37kg) were divided into 6 pens, 14 pigs per pen (7 gilts and 7 barrows per pen). 3 pens of pigs were fed with control diet (corn-soybean meal) and the others were fed control diet addition with 50 mg/kg NMA. During the trial, all pigs were given free access to feed and water. After 44 days trial, 8 pigs from each treatment (4 gilts and 4 barrows, weight similar to average group weight, $86.94{\pm}0.71kg$ for control group, and $90.55{\pm}1.51kg$ for NMA treated group) were sacrificed to collect the sample of the liver, longissimus muscle, subcutaneous fat (10th rib). The addition of NMA in diet increased the IGF-I, Insulin, T3, T4 levels in serum by 50.68% (p<0.05), 38.36% (p<0.05), 123.33% (p<0.01), 60.58% (p<0.03), respectively. Meanwhile, IGF-I level in the liver and the muscle were increased with 17.83% (p<0.03) and 26.00% (p<0.03) with addition of NMA. The data from subcutaneous fat (10th rib) analysis showed that supplement of 50 mg/kg NMA decreased the total activities of malic dehydrogenase (MDH) by 20.54% (p<0.05), glucose-6- phosphate dehydrogenase (G-6-DPH) by 16.97% (p<0.05), and decreased the specific activities of MDH and G-6-DPH by 37.46% (p<0.01) and 35.06% (p<0.01), respectively. The hormone sensitive lipase (HSL) total activity was increased by 25.00% (p<0.05) in NMA treated pigs. These results indicated that addition of 50 mg/kg NMA to diet can induce the endocrine great change in finishing pigs, furthermore, inhibit the fat synthesis through suppressing lipogenic enzymes and promote the fat degradation by elevating HSL activity in finishing pigs.
Brassinosteroids (BRs) are a special class of plant steroid hormones that are essential for normal growth and development. Part of confusion is whether BRs are unique to plants, because they have overlapping physiological roles with other better-studied hormones and with physiological responses caused by light. In systems designed to assay for cytokinins, the effects of BRs vary. We measured hypocotyl length for testing the ability of brassinolide (BL) to rescue double mutant between det2 and the photoreceptor null mutant phytochrome B (phyB). PHYB involved in controlling hypocotyl elongation in increased concentration of BL whereas phyBdet2 double mutant just partially rescue to phyB in white and red light indicated the involvement of BRs in PHYB regulated cell elongation. BRs regulated hypocotyl growth was delayed by BAP, a cytokinin treatment but inhibitory effects of BAPs on hypocotyl growth was slightly recovered by BL. The result indicated that the mode of action of BR and cytokinin is independent or sequential in the downstream light-regulated response control on hypocotyl elongation and also light modulated the action of BR and cytokinin in some extent.
Kim, Jae-Hyun;Chung, Hye-Rim;Lee, Young-Ah;Lee, Sun-Hee;Kim, Ji-Hyun;Shin, Choong-Ho;Yang, Sei-Won
Clinical and Experimental Pediatrics
/
v.52
no.8
/
pp.922-929
/
2009
Purpose : The aim was to investigate the clinical characteristics and responses to growth hormone (GH) therapy in children with attenuated growth who showed normal GH responses to GH stimulation tests (GHST). Methods : The study included 39 patients with height velocity (HV) of less than 4 cm/yr and normal GHST results. Clinical characteristics of patients were analyzed retrospectively. Results : Eleven were born as small for gestational age (SGA) and 28 as appropriate for age (AGA). In the SGA group, the standard deviation score (SDS) of age and height measured at their first visit was significantly low. Sixteen patients were treated with GH and six of 23 without GH therapy were followed for 1 year after GHST. The mean (range) of HV was 7.7 (4.9 to 11.1) cm/yr in patients with GH therapy and 3.7 (2.7 to 4.5) cm/yr in those without GH therapy, which was statistically significant (P<0.001). In the GH-treated group, HV and difference in height SDS during the treatment increased significantly (P<0.001; P< 0.001, respectively). HV increased after 1 year of GH therapy in the SGA and AGA groups (SGA, P=0.043; AGA, P=0.003). The level of Insulin-like growth factor-I was significantly lower in GH-treated patients with height SDS <-3 than those with ${\geq}3$ (P=0.023). Conclusion : In children with growth failure and normal GHST, HV increases significantly by short-term GH therapy. The assessment of long-term effects of GH therapy is necessary. Moreover, further studies should be considered to evaluate the GH-IGF-I axis due to the possibility of GH insensitivity syndrome.
Objectives: The purpose of this study was to evaluate the effects of 12 weeks walking exercise program participation on changes in aging-related hormones concentration in elderly men. Methods: 16 elderly men(above 65 years old) were participated in 12 weeks walking exercise program by group types(exercise group ; n=8 & control group ; n=8), and their aging-related hormones(GH, testosterone and melatonin) levels were assessed before program(0 week) and after program(12 weeks). Regularly walking exercise program(field walking exercise) performed for 12 weeks(3days/week, 60~70min/day, HRR 55~65%). All data were expressed as mean and standard deviation by using SPSS/$PC^+$(ver. 13.0) program, and to evaluate the differences before and after treatment by groups, data were analyzed by paired t-test(a${\leq}$.05) and 2-way ANOVA was performed to examine the differences between groups and within groups by variables. Results and Conclusion: The conclusions obtained from this study were as follows ; In growth hormone. testosterone and melatonin response after 12 weeks exercise was increased significantly in walking exercise group(p<.01; p<.001; p<.001). And in result of 2-way ANOVA analysis for group, exercise, group${\times}$exercise, as compared with the exercise, there is significant difference in all items. Interaction effect of between group and exercise is difference significantly on GH(F=5.915, p<.05), testosterone(F=15.117, p<.01) and melatonin(F=8.131. p<.01) in all groups. We observed a direct relationship(positive improvement) between the regular physical activity and aging-related hormones(growth hormone, testosterone and melatonin concentrations) in elderly men.
The production and secretion of growth hormone (GH) in the anterior pituitary gland can be induced by several natural products to control cell proliferation, differentiation, and migration. To investigate whether Chungkookjang (CKJ) produced by the fermentation process affects GH-related metabolism, the secretion and the response of GH were observed in pituitary cells and GH target cells. Among six CKJs manufactured by different strains of glycine max, only three CKJs, including Daewon (DW), Daepung (DP), and Taegwang (TG), induced GH secretion from GH3 cells at 5.0 mg/ml concentration. There were no significant changes detected in the viability of any of the cells treated with these CKJs. In addition, the increase in GH secretion from the GH3 cells was dependent on the concentration of the three types of CKJs. The proliferation of cell lines, including MG63 and HepG2 cells, that originated from those derived from the GH target organs was significantly activated by treatment with the GH-containing conditional medium (GCM) harvested from the three CKJ-treated GH3 cells, although their induction rate was different from each other. In these cells, p-STAT5 was maximally translocated into the nucleus of MG63 cells 30 min after DW treatment, while it was translocated in HepG2 cells at 60 min. These results suggest that these three types of CKJ could enhance the secretion of GH, as well as the GCM-derived response, in the two target organs.
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