• Clinical and Experimental Pediatrics
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• v.50 no.7
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• pp.678-685
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• 2007

Purpose : Recent reports pointed out that gonadotropin releasing hormone analogue (GnRHa) therapy alone is not so promising for improving adult height in precocious puberty. So, that we studied the growth promoting effect of combined therapy with GnRHa and growth hormone (GH) in early pubertal girls. Methods : Twenty three early pubertal girls ($9.73{\pm}1.59yr$) with predicted adult heights (PAH) below-2 standard deviation score (SDS) were included. They were divided into two groups as follows; Group I before menarche (n=19) and Group II after menarche (n=4). After combined therapy, various growth parameters were compared between two groups and between the before and after therapy. Results : Between the two groups before therapy, chronologic age (CA), growth velocity (GV), body mass index (BMI), target height (TH), PAH and serum insulin-like growth factor binding protein-3 were not different, but BA, height and difference between bone age (BA) and CA were significantly higher and insulin-like growth factor-1 (IGF-1) was marginally higher in group II. After therapy, BA still remained higher in group II, but other parameters were not different. In both groups, after therapy, the difference between BA and CA, the ratio of BA over CA, and GV were significantly decreased, but PAH, height SDS and BMI were significantly increased. Regarding IGF-1 level, a significant increase was noted in group I, but not in group II. Conclusion : With combined therapy of GnRHa and GH, PAH in early pubertal girls might be improved significantly and even approach TH. Among them, those who were before menarche might have greater potential for the height gain than those after menarche in view of IGF-1 changes during therapy.

• Development and Reproduction
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• v.10 no.2
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• pp.97-103
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• 2006

Vitellogenin(Vg) is a sex specific serum protein present in sexually maturing female blood of oviparous vertebrates. Estrogen($E_2$) is a main inducer of hepatic Vg synthesis. We investigated the effects of androgen and growth hormone(GH) on regulation of Vg and estrogen receptor(ER) genes in Japanese eel. Immature eels($200{\sim}250\;g$) were given a single injection of $E_2(5{\sim}5,000\;{\mu}g/kg\;bw)$ alone, or in combination with eel recombinant GH(eGH, $1{\sim}10\;{\mu}g/kg$) or methyltestosterone(MT, $1{\sim}5\;mg/kg$) and sacrificed 10 days after the hormone treatments. Expression levels of ER and Vg genes from the liver were determined by means of reverse transcription and polymerase chain reaction(RT-PCR). Administration of $E_2$ stimulated Vg gene expression in a dose dependent manner. Levels of Vg mRNA after the injection of $E_2(500\;{\mu}g/kg)$ with MT(5mg/kg) or eGH($10\;{\mu}g/kg$) were much higher than in that of $E_2$ alone($500\;{\mu}g/kg$). Whereas, injection of either vehicle, eGH ($10\;{\mu}g/kg$) or MT(5mg/kg) alone did not induce the expression of Vg gene in the liver. ER mRNA was detected from the fish treated with vehicle alone. $E_2$ injection($5{\sim}500\;{\mu}g/kg\;bw$) increased this ER expression but dose dependent response was not clear. Addition of MT(5mg/kg) or eGH($10\;{\mu}g/kg$) did not affect $E_2-stimulated$ ER mRNA expression. This study confirms the necessity of $E_2$ as the primary factor for Vg gene expression and requirement of additional hormones such as MT or GH for the full expression of Vg mRNA, and suggests that the additive effect of MT or GH on Vg gene expression would be mediated by some unknown factors other than ER.

• Clinical and Experimental Pediatrics
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• v.46 no.4
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• pp.363-369
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• 2003

Purpose : Pharmacologic provocation test of growth hormone(GH) is a non-physiologic method and has several limitations for diagnosing growth hormone(GH) deficiency. Spontaneous GH release studies could be important in understanding the pathophysiology of children with poor growth but normal responses to GH provocation tests. Also, the relationship between nocturnal GH secretions and sleep patterns in short stature children is poorly understood. The aim of this study is to determine whether there are differences in sleep patterns and nocturnal GH secretory profiles between idiopathic short stature children and a normal stature group. Methods : Spontaneous nocturnal GH secretions and sleep patterns were evaluated in 12 prepubertal idiopathic short stature children with normal responses to provocation tests and 9 normal stature controls. Blood samples were taken every 30 minutes from 22:00-06:30 and sleep patterns were analyzed by polysomnography. Results : The mean GH level during sleep was significantly lower in short stature children than in controls. The peak GH level after sleep, coincident with the first slow wave sleep, was lower in the short stature group. The slow wave sleep times of short stature children were decreased compared with those of normal subjects. Conclusion : These results suggest that overnight serial GH sampling is helpful to identify short stature children with subnormal GH secretions, and sleep structure differences may be associated with decreased overnight GH secretions in short stature children.

• Korean Journal of Animal Reproduction
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• v.18 no.3
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• pp.175-182
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• 1994

Rat $\beta$-casein 유전자와 사람 성장호르몬 (hGH) 유전자의 융합유전자를 생쥐 수정란의 웅성전핵에 미세주입하여 형질전환생쥐 (transgenic mouse) 6계통을 확립하였다. 이들로부터 사람성장호르몬(hGH) 유전자의 발현 여부를 조사한 결과, 6계통중 4계통의 생쥐 유즙에서 hGH가 2~900 ng/ml 수준으로 발현되고 있었으며, 혈중에서는 hGH가 검출되지 않았다. 따라서 이들 형질전환생쥐에서 사람성장호르몬이 우선특이적으로 발현, 분비되고 있음을 알 수 있었다. 한편, 사람성장호르몬의 발현이 확인된 두 계통 (ChGH2-2, CChGH2)의 형질전환생쥐를 대상으로 하여 세대별, 산차별로 유즙내 사람성장호르몬의 함량을 조사한 결과, 3세대에 걸쳐, 또한 제1세대에서의 세차례 반복된 비유기에도 유즙내 사람성장호르몬은 지속적으로 분비되고 있었다. 이상의 결과는 형질전환생쥐에서의 외래유전자의 발현성은 반복되는 비유기와 여러 세대에 걸쳐 안정적으로 유지됨을 보여 주고 있다.

• 대한생식의학회:학술대회논문집
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• 1995.12a
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• pp.70.1-70.1
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• 1995

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.5
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• pp.217-223
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• 2008

To directly test if elevated glucocorticoids are required for fasting-induced regulation of growth hormone (GH)-releasing hormone (GHRH), GHRH receptors (GHRH-R) and ghrelin receptors (GHS-R) expression, male rats were bilaterally adrenalectomized or sham operated. After 7 days, animals were fed ad libitum or fasted for 48 h. Bilateral adrenalectomy increased hypothalamic GHRH to 146% and decreased neuropeptide Y (NPY) mRNA to 54% of SHAM controls. Pituitary GHRH-R and GHS-R mRNA levels were decreased by adrenalectomy to 30% and 80% of shamoperated controls. In shamoperated rats, fasting suppressed hypothalamic GHRH (49%) and stimulated NPY (166%) mRNA levels, while fasting increased pituitary GHRH-R (391%) and GHS-R (218%) mRNA levels. However, in adrenalectomized rats, fasting failed to alter pituitary GHRH-R mRNA levels, while the fasting-induced suppression of GHRH and elevation of NPY and GHS-R mRNA levels remained intact. In fasted adrenalectomized rats, corticosterone replacement increased GHRH-R mRNA levels and intensified the fasting-induced decrease in GHRH, but did not alter NPY or GHS-R response. These data suggest that elevated glucocorticoids mediate the effects of fasting on hypothalamic GHRH and pituitary GHRH-R expression, while glucocorticoids are likely not the major determinant in fasting-induced increases in hypothalamic NPY and pituitary GHS-R expression.

• Journal of Interdisciplinary Genomics
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• v.5 no.2
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• pp.18-23
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• 2023

Conventional evaluation method for identifying the organic cause of short stature has a low detection rate. If an infant who is small for gestational age manifests postnatal growth deterioration, triangular face, relative macrocephaly, and protruding forehead, a genetic testing of IGF2, H19, GRB10, MEST, CDKN1, CUL7, OBSL1, and CCDC9 should be considered to determine the presence of Silver-Russell syndrome and 3-M syndrome. If a short patient with prenatal growth failure also exhibits postnatal growth failure, microcephaly, low IGF-1 levels, sensorineural deafness, or impaired intellectual development, genetic testing of IGF1 and IGFALS should be conducted. Furthermore, genetic testing of GH1, GHRHR, HESX1, SOX3, PROP1, POU1F1, and LHX3 should be considered if patients with isolated growth hormone deficiency have short stature below -3 standard deviation score, barely detectable serum growth hormone concentration, and other deficiencies of anterior pituitary hormone. In short patients with height SDS <-3 and high growth hormone levels, genetic testing should be considered to identify GHR mutations. Lastly, when severe short patients (height z score <-3) exhibit high levels of prolactin and recurrent pulmonary infection, genetic testing should be conducted to identify STAT5B mutations.

• Clinical and Experimental Pediatrics
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• v.52 no.11
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• pp.1249-1259
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• 2009

Purpose:From a societal perspective, we evaluated the cost-effectiveness of a novel sustained-release injection of recombinant human growth hormone (GH) administered on a weekly basis compared with that of the present daily GH injection for the treatment of children with GH deficiency. Methods:Health-related utility for GH therapy was measured based on the visual analogue scale. During July 2008, caregivers of 149 children receiving GH therapy form 2 study sites participated in a web-based questionnaire survey. The survey required the caregivers to rate their current subjective utility with daily GH injections or expected utility of weekly GH injections. Because there was no difference in the costs of the daily and weekly therapies, for the purposes of this study, only drug acquisition costs were considered. Results:Switching from daily to weekly injection of GH increased the utility from 0.584 to 0.784 and incurred an extra cost of 4,060,811 Korean won (KW) per year. The incremental cost-utility ratio (ICUR) for a base case was 20,305,055 KW per quality-adjusted life year (QALY) gained. Scenario analyses showed that the ICUR ranged from 15,751,198 to 25,489,929 KW per QALY. Conclusion:The ICUR for a base case and worst case scenario analyses ranged from 0.85 to 1.37-times per capita gross domestic product of Korea, which is considered to be within the generally accepted willingness-to-pay threshold. Thus, it is concluded that switching from daily to weekly injection of GH would be cost-effective.

• Biomolecules & Therapeutics
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• v.3 no.4
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• pp.294-300
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• 1995

DA-3002, an authentic recombinant human growth hormone(rhGH), was examined for mutagenicity in the reverse mutation test on bacteria, in the chromosomal aberration test on cultured mammalian cells and in the micronucleous test on mice. The reverse mutation test was performed by a plate incorporation method with or without a metabolic activation system(S9 Mix) using Salmonella typhimurium strain TA100, TA1535, TA98 and TA1537. DA-3002 did not significantly increase revertant colonies in any of the test strains under any conditions at dose levels ranging from 0.0125 to 0.4 IU/plate, compared with the vehicle control. In the chromosomal aberration test using cultured Chinese hamster lung(CHL) cells, DA-3002 did not increase the number of aberrant cells in the presence or absence of S9 mix at concentrations of 0.0125 IU/mι to 0.4 IU/mι, compared with the vehicle control. In the micronucleus test, male ICR mice were given DA-3002 intraperitoneally at a dose level of 20, 40 and 80 lU/kg. The incidence of bone marrow micronucleated polychromatic erythrocytes in the DA-3002 treated mice did not differ from that of the vehicle control. These results indicate that DA-3002 doesn't have mutagenic potential under the present test conditions.

• Journal of Korean Neurosurgical Society
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• v.56 no.5
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• pp.405-409
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• 2014

Objective : To determine the efficacy of endoscopic surgery in combination with long-acting somatostatin analogues (SSAs) in treating patients with growth hormone (GH)-secreting pituitary tumor. Methods : We performed retrospective analysis of 133 patients with GH producing pituitary adenoma who underwent pure endoscopic transsphenoidal surgery in our center from January 2007 to July 2012. Patients were followed up for a range of 3-48 months. The radiological remission, biochemical remission and complication were evaluated. Results : A total of 110 (82.7%) patients achieved radiological complete resection, 11 (8.2%) subtotal resection, and 12 (9.0%) partial resection. Eighty-eight (66.2%) patients showed nadir GH level less than 1 ng/mL after oral glucose administration. No mortality or severe disability was observed during follow up. Preoperative long-acting SSA successfully improved left ventricle ejection fraction (LVEF) and blood glucose in three patients who subsequently underwent success operation. Long-acting SSA (20 mg every 30 days) achieved biochemical remission in 19 out 23 (82.6%) patients who showed persistent high GH level after surgery. Conclusion : Endoscopic transsphenoidal surgery can biochemically cure the majority of GH producing pituitary adenoma. Post-operative use of SSA can improve biochemical remission.