• Korean Journal of Animal Reproduction
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• v.26 no.4
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• pp.395-399
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• 2002

Human chorionic gonadotropin (hCG) is a member of the glycoprotein hormone family which includes FSH. hCG TSH. These hormone family is characterized by a heterodimeric structure composed a common $\alpha$-subunit noncovalently linked to a hormone specific $\beta$-subunit. To determine u and $\beta$ -subunits can be synthesized as a single polypeptide chain (tethered-hCG) and also display biological activity, the tethered-hCC and -FSH molecule by fusing the carboxyl terminus of the hCG $\beta$-subunit to the amino terminus of the $\alpha$-subunit was constructed. To determine the importance of $\alpha$ COOH -terminal amino acid, we also deleted the $\alpha$ COOH-terminal amino acids. The expressing vectors were transfected into CHO-K 1 cells. The tethered-wthCG and -wtFSH was efficiently secreted. The $\alpha$ Δ83hCG and $\alpha$ Δ 83FSH mutants had no secretion. These results are the first conclusive evidence that COOH-terminal amino acids are very important for secretion in human glycoprotein hormone $\alpha$-subunit. These results demonstrated that the $\alpha$ Δ83hCG and $\alpha$ Δ 83FSH mutants could be play a pivotal role in the secretion of tethered-molecule.

• Journal of mucopolysaccharidosis and rare diseases
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• v.4 no.2
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• pp.42-44
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• 2018

Prader-Willi syndrome (PWS) is a multisystemic complex disorder characterized by hyperphagia and impaired satiety which lead to severe and early obesity. In infancy, hypotonia and poor suck are main problems, and a child goes through Failure-to-thrive. During childhood, clinical manifestations change to food seeking as well as excessive weight gain, short stature, developmental delay, cognitive disability and behavioral problems. Also, growth hormone insufficiency is frequent. Most patients receive the recombinant growth hormone (rGH) therapy that provides improvement in growth, body composition, and physical attributes. The clinical care guideline for rGH therapy in PWS had been noticed in 2013. The rGH therapy helps in body fat, lean body mass, height SDS and head circumference. Also, the rGH therapy helps motor function, psychomotor development and cognition and behavioral issues.In Samsung medical center, there are clinical care guidelines for rGH therapy in PWS and an useful application for the patients. 'Living with PWS', the name of an moblie application for PWS patients, was introduced in the lecture. The application revised to version 2. It was made more convenient to users than in version 1. It helps caregivers to schedule the rGH therapy and to monitor height and weight.

• 한국생물공학회:학술대회논문집
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• 2005.04a
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• pp.37-37
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• 2005

Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone consisting of non-covalently linked two subunits, the ${\alpha}$ and ${\beta}$ subunit. It has been used as a infertility drug for ovulation to mimic luteinizing hormone $(LH).^{1)}$ A stable cell line was established by transfection of Rc/CMV-i-dhfr-hCG, expression vector containing hCG ${\alpha}-$ and ${\beta}-genes$, into dihydrofolate reductase-deficient CHO cells and subesquent methotrexate-mediated gene amplification. Anchorage-dependent CHO cells were adapted into a serum-free and/or animal component-free suspension medium through gradual serum weaning for the hCG production. The established cell line showed typical morphological characteristics and growth profile of CHO cells, and could produce FSH with passage-to-passage consistency. The high density perfusion culture of the CHO cells was carried out in Celligen Plus bioreactor equipped with a spin-filter as a internal cell retention device. The cell density reached up to $>1x10^{7}$ cells/ml in less than 7 days and a perfusion-control strategy based on cellular consumption rates of glucose was $established.^{2)}$ Biologically active recombinant hCG was purified by a series of chromatographic steps including anion exchange chromatography and hydrophobic interaction chromatography to homogeneity. The highly purified recombinant hCG was characterized for physicochemical, immunological and biological properties.

• Journal of Aquaculture
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• v.20 no.3
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• pp.154-159
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• 2007

Manchurian trout (Brachymystax lenok) is an endangered fish species in East Asia including the Korean peninsula. To establish a method for artificial propagation and to improve our understanding of the reproduction in the species, we have produced recombinant gonadotropins, follicle-stimulating hormone (r-mtFSH) and luteinizing hormone (r-mtLH), which may play central roles in reproductive activities. In the present study, the biological activities of the recombinant hormones were analyzed by gonadosomatic index (GSI), ovarian follicle diameter, and sex steroid levels in mature rainbow trout (Oncorhynchus mykiss). In the 6th day post-injection, FSH-injected fish were slightly decreased in the GSI value, although there were no significant differences among those of control, r-mtFSH, and r-mtLH treatments. Injection of the r-mtFSH increased follicle diameters significantly as compared with those of control- and r-mtLH-injected fish. The plasma steroid levels showed wide differences in the groups at 1, 3, or 6th day post-injection. Despite the variable steroid levels, three individuals receiving either r-mtFSH or r-mtLH showed a great increase in a maturation-inducing steroid, $17{\alpha},20{beta}$-dihydroxy-4-pregnen-3-one, at 3 and 6 days. Taken together, these results suggest that biological efficacies of the recombinant FSH and LH should be further studied in the Manchurian trout.

• Clinical and Experimental Pediatrics
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• v.62 no.7
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• pp.274-280
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• 2019

Purpose: To analyze the growth response to growth hormone (GH) therapy in prepubertal patients with Noonan syndrome (NS) harboring different genetic mutations. Methods: Twenty-three patients with prepubertal NS treated at Pusan National University Children's Hospital between March 2009 and July 2017 were enrolled. According to the disease-causing genes identified, the patients with NS were divided into 4 groups. Three groups were positive for mutations of the PTPN11, RAF1, and SOS1 genes. The five genes undetected (FGU) group was negative for PTPN11, RAF1, SOS1, KRAS, and BRAF gene mutations. The influence of genotype was retrospectively analyzed by comparing the growth parameters after GH therapy. Results: The mean chronological age at the start of GH treatment was $5.85{\pm}2.67years$. At the beginning of the GH treatment, the height standard deviation score (SDS), growth velocity (GV), and lower levels of insulin-like growth factor-1 (IGF)-1 levels were not statistically different among the groups. All the 23 NS patients had significantly increased height SDS and serum IGF-1 level during the 3 years of treatment. GV was highest during the first year of treatment. During the 3 years of GH therapy, the PTPN11, RAF1, and SOS1 groups showed less improvement in height SDS, IGF-1 SDS, and GV, and less increase in bone age-to-chronological age ratio than the FGU group. Conclusion: The 3-year GH therapy in the 23 prepubertal patients with NS was effective in improving height SDS, GV, and serum IGF-1 levels. The FGU group showed a better response to recombinant human GH therapy than the PTPN11, RAF1, and SOS1 groups.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.50 no.2
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• pp.103-109
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• 2024

Teriparatide has been effective in treating people diagnosed with medication-related osteonecrosis of the jaw (MRONJ). However, its efficacy is not well established to be accepted as a standard of care. The objective of this paper was to investigate the efficacy of recombinant human parathyroid hormone for the treatment of MRONJ. We report three cases of MRONJ patients with osteoporosis as the primary disease who were treated with a teriparatide agent along with other adjunctive measures. Each patient was administered a teriparatide injection subcutaneously for 16 weeks, 36 weeks, or 60 weeks. Surgical intervention including partial resection, sequestrectomy, decortication, and saucerization took place during the teriparatide administration. Complete lesion resolution was identified clinically and radiographically in all three patients. In patients diagnosed with MRONJ, teriparatide therapy is an efficacious and safe therapeutic option to improve healing of bone lesions. These findings demonstrate that teriparatide in combination with another therapy, especially bone morphogenetic protein, platelet-rich fibrin, or antibiotic therapy, can be an effective protocol for MRONJ.

• Clinical and Experimental Pediatrics
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• v.53 no.9
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• pp.845-851
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• 2010

Purpose: Recombinant human growth hormone (rhGH) has been widely used to treat short stature. However, there are some concerns that growth hormone treatment may induce skeletal maturation and early onset of puberty. In this study, we investigated whether rhGH can directly affect the neuronal activities of of gonadotropin-releasing hormone (GnRH). Methods: We performed brain slice gramicidin-perforated current clamp recording to examine the direct membrane effects of rhGH on GnRH neurons, and a whole-cell voltage-clamp recording to examine the effects of rhGH on spontaneous postsynaptic events and holding currents in immature (postnatal days 13-21) and adult (postnatal days 42-73) mice. Results: In immature mice, all 5 GnRH neurons recorded in gramicidin-perforated current clamp mode showed no membrane potential changes on application of rhGH (0.4, $1{\mu}g/mL$). In adult GnRH neurons, 7 (78%) of 9 neurons tested showed no response to rhGH ($0.2-1{\mu}g/mL$) and 2 neurons showed slight depolarization. In 9 (90%) of 10 immature neurons tested, rhGH did not induce any membrane holding current changes or spontaneous postsynaptic currents (sPSCs). There was no change in sPSCs and holding current in 4 of 5 adult GnRH neurons. Conclusion: These findings demonstrate that rhGH does not directly affect the GnRH neuronal activities in our experimental model.

• Clinical and Experimental Reproductive Medicine
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• v.29 no.1
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• pp.45-56
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• 2002

Objectives: Recently, recombinant FSH (rFSH) has been manufactured using a Chinese hamster ovary cell line transfected with the gene encoding human FSH. Both rFSH and urinary gonadotropin (uFSH) could be used for controlled ovarian hyperstimulation (COH). However, uFSH implies a number of disadvantages, such as batch-to-batch inconsistency, no absolute source control, dependence on large amounts of urine, low specific activity, and low purity. The purpose of this study was to evaluate the efficacy of rFSH in human IVF-ET program. Materials and Methods: A total of 508 infertile women was enrolled in this study. They are classified into rFSH group (n=177) or uFSH group (n=331), and all of them were matched by age and cause of infertility in same period. The $Puregon^{(R)}$ (Organon, Holland) was used as rFSH, and the Metrodin-$HP^{(R)}$ (Serono, Switzeland) and $Humegon^{(R)}$ (Organon, Holland) was used as uFSH. We subdivided the patients into three age groups. The outcomes of IVF-ET program were analyzed using the statistical package for social sciences (SPSS). Results: There was no significant differences in the level of estradiol on hCG injection day, the numbers of retrieved oocytes, matured oocytes, fertilized oocytes, transferred embryos, frozen embryos between the two groups. The total dose (IU) of gonadotropin for COH was significantly lower in the rFSH group compared to uFSH group ($1339{\pm}5491.1$ vs $2527.8{\pm}1075.2$ IU, p<0.001). Clinical pregnancy rate per embryo transfer in the rFSH group showed increasing tendency, compared to the uFSH group, but there was no statistical significance (35.2% vs 29.3%). Our results demonstrated that the relative efficiency of rFSH compared with uFSH is higher in older patients. Conclusions: The ovarian stimulatory effect and clinical outcome of recombinant FSH was similar to that of the urinary gonadotropin. The IVF-ET cycles with significantly lower dose of gonadotropin in rFSH group showed comparable results. Therefore, we suggest that recombinant FSH is more potent and effective than urinary gonadotropin.

• Childhood Kidney Diseases
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• v.10 no.2
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• pp.142-151
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• 2006

Purpose : Growth retardation is one of the serious problems in children with nephropathy requiring long-term steroid therapy. We observed the efficacy and safety of recombinant human growth hormone(rhGH) on the growth in children with long-term steroid therapy. Methods : We studied 60 children(male 47, female 13) with nephropathy who received rhGH(1 U/kg/week) for more than 0.5 years($1.39{\pm}1.12$). Their mean age was 11.0 years($11.17{\pm}2.62$). They received steroid therapy from January 1987 through July 2005, and the mean duration of steroid therapy was $4.32{\pm}2.97$ years. Among the patients, there were 32 nephrotic syndrome, 9 IgA nephropathy, 4 mesangial proliferative glomerulonephritis, 4 focal segmental glomerulosclerosis, 2 Henoch $Sch\ddot{o}nlein$ nephritis, 2 Alport syndrome and 7 other cases. Data were gathered on the growth parameters, such as growth velocity, height standard deviation score(SDS), IGF-1, IGFBP-3, bone mass density(BMD) and general chemistry changes. Results : Height velocity increased significantly with rhGH therapy from $3.29{\pm}1.95$ to $8.66{\pm}3.75$(cm/yr) and height SDS decreased from $-0.72{\pm}0.93$ to $-1.04{\pm}0.86$ at one year after steroid therapy but increased to $-0.55{\pm}0.96$ at one year after rhGH administration(P<0.05). BMD improved from $0.71{\pm}0.14$ to $0.79{\pm}0.15g/cm^2$(P<0.05). IGF-1 increased from $445.09{\pm}138.01$ to $506.62{\pm}181.31ng/mL$(P<0.05). IGFBP-3 decreased from $4073.75{\pm}700.78$ to $3933.61{\pm}789.25ug/L$ numerically, but there was no statistically significant difference(P=0.533). Conclusion : The administration of rhGH in the short stature patients who received long-term steroid therapy showed improvement in growth parameters such as SDS, growth velocity, and BMD without significant side-effects or changes in the biochemical parameters.

• Fisheries and Aquatic Sciences
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• v.11 no.4
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• pp.183-189
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• 2008

In this study, tests were conducted to investigate the effects of three dietary growth hormones, administered in various amounts, on the growth performance and lysozyme activity in juvenile olive flounder, Paralichthys olivaceus. Three dietary growth hormones, recombinant human growth hormone (rHGH), recombinant bovine somatotropin A (rBST A) and recombinant bovine somatotropin B (rBST B) were tested at three different supplemental levels (10, 20 or 40 mg/kg body weight per week) by a $3{\times}3$ factorial design and a complete randomized design in comparison to a control group. Fish were fed one of the ten experimental diets (control, $rHGH_{10}$, $rHGH_{20}$, $rHGH_{40}$, rBST $A_{10}$, rBST $A_{20}$, rBST $A_{40}$, rBST $B_{10}$, rBST $B_{20}$ and rBST $B_{40}$) for 6 weeks and afterward were analyzed for growth performance by measuring weight gain (WG), feed efficiency (FE), specific growth rate (SGR) and protein efficiency ratio (PER). Based on the factorial design analysis, fish fed rHGH diets demonstrated significantly higher growth performance than fish fed rBST A or rBST B diets. However there were no significant differences in WG, FE, SGR and PER between fish fed rBST A and rBST B diets. Neither hormone level nor the interaction between the different hormones and their various levels had a significant effect on WG, FE, SGR, PER, lysozyme activity or whole-body proximate composition. A complete randomized design analysis confirmed fish fed $rHGH_{10}$, $rHGH_{20}$, $rHGH_{40}$, rBST $A_{10}$, rBST $A_{20}$, rBST $A_{40}$, rBST $B_{20}$ and rBST $B_{40}$ diets for 6 weeks showed higher WG than fish fed the control diet (P<0.05). A higher FE was observed in fish fed $rHGH_{10}$, $rHGH_{20}$, $rHGH_{40}$, rBST $A_{20}$ and rBST $A_{40}$ diets in comparison to fish fed the control diet. Fish fed all graded rHGH, rBST A and rBST B supplemented diets showed a higher SGR than fish fed the control diet. Regarding PER, fish fed $rHGH_{10}$, $rHGH_{20}$, $rHGH_{40}$, rBST $A_{10}$, rBST $A_{20}$, rBST $A_{40}$ and rBST $B_{20}$ diets were higher than fish fed the control diet. Furthermore, the lysozyme activity of fish fed a diet of $rHGH_{20}$ was significantly higher than that of fish fed any other diet. The results measuring the growth and development of the fish clearly suggest the biopotency of dietary rHGH could be higher than those of both dietary rBST A and rBST B. Further implied is the probability that within the range of 10 to 40 mg/kg BW/week the dietary growth hormones could accelerate growth performance, and that 20 mg rHGH/kg BW/week could possibly enhance lysozyme activity in juvenile olive flounder, Paralichthys olivaceus.