• Clinical and Experimental Pediatrics
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• v.49 no.3
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• pp.305-311
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• 2006

Purpose : GnRH analogues(GnRHa) are used to treat central precocious puberty(CPP). However, in some patients, the GV decrease is so remarkable that it impairs predicted adult height(PAH); and there fore, the addition of growth hormone(GH) is suggested. We analysed the growth changes during two years and final adult height(FAH) in girls with idiopathic CPP treated with combined therapy, compared with those of girls treated with GnRHa alone. Methods : For the analysis, we classified the patients, who was treated for longer than two years, into three groups depending on the initial PAH and combination of GH; PAH_L, treated with GnRHa and PAH less than midparental height(MPH) - 5 cm. PAH_H, treated with GnRHa and PAH greater than MPH - 5 cm. GnRHa＋GH, combined GH treatment, regardless of PAH before treatment. We analysed the GV and PAH change during the first two years and FAH. Results : In PAH_L, the PAH(SDS) at first year of therapy was significantly increased to $153.5{\pm}6.5cm(-1.4{\pm}1.3)$ from $149.7{\pm}6.4cm(-2.1{\pm}1.3)$ before treatment(P=0.004). In PAH_H, there was no significant increase in PAH during the two years of treatment. During the first year of combination of GH and GnRHa, GV and PAH increased significantly. We observed significant increases in FAH, comparing to the initial PAH in the PAH_L and GnRHa＋GH groups. The height gains(FAH - initial PAH) were significantly higher in the PAH_L and GnRHa＋GH groups than that in the PAH_H group. Conclusion : This study suggests the FAH and height gains are improved in patients, whose predicted adult height before treatment was shorter than those with higher predicted adult height, with the treatment of GnRHa alone or in combination with GH. GH could not improve the final adult height, but compensated the growth in patients whose growth velocity was decelerated by GnRHa alone.

• Development and Reproduction
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• v.13 no.4
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• pp.257-264
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• 2009

A neurotoxin, 6-hydroxydopamine (6-OHDA) has been widely used to create animal model for Parkinson's disease (PD) due to its specific toxicity against dopaminergic (DA) neurons. Since DA signals modulate a broad spectrum of CNS physiology, one can expect profound alterations in neuroendocrine activities of both PD patients and 6-OHDA treated animals. Limited applications of 6-OHDA injection model, however, have been made on the studies of hypothalamuspituitary neuroendocrine circuits. The present study was performed to examine whether blockade of brain catecholamine (CA) biosynthesis with 6-OHDA can make any alteration in the transcriptional activities of hypothalamus-pituitary hormone genes in adult male rats. Three-month-old male rats (SD strain) were received 6-OHDA ($200{\mu}g$ in $10{\mu}\ell$ of saline/animal) by intracerebroventricular (icv) injection, and sacrificed after two weeks. To determine the mRNA levels of hypothalamuspituitary hormone genes, total RNAs were extracted and applied to the semi-quantitative RT-PCRs. The mRNA levels of tyrosine hydroxylase (TH), the rate-limiting enzyme for the catecholamine biosynthesis, were significantly lower than those from the control group (control:6-OHDA=1:0.72${\pm}$0.02AU, p<0.001), confirming the efficacy of 6-OHDA injection. The mRNA levels of gonadotropin-releasing hormone (GnRH) and corticotropin releasing hormone (CRH) in the hypothalami from 6-OHDA group were significantly lower than those from the control group (GnRH, control:6-OHDA=1:0.39${\pm}$0.03AU, p<0.001; CRH, control:6-OHDA=1:0.76${\pm}$0.07AU, p<0.01). There were significant decreases in the mRNA levels of common alpha subunit of glycoprotein homones (Cg$\alpha$), LH beta subunit (LH-$\beta$), and FSH beta subunit (FSH-$\beta$) in pituitaries from 6-OHDA group compared to control values (Cg$\alpha$, control:6-OHDA=1:0.81${\pm}$0.02AU, p<0.001; LH-$\beta$, control:6-OHDA=1:0.68${\pm}$0.04AU, p<0.001; FSH-$\beta$, control:6-OHDA=1:0.84${\pm}$0.05AU, p<0.001). Similarly, the level of adrenocorticotrophic hormone (ACTH) transcripts from 6-OHDA group was significantly lower than that from the control group (control: 6-OHDA=1:0.86${\pm}$0.04AU, p<0.01). The present study demonstrated that centrally injected DA neurotoxin could downregulate the transcriptional activities of the two hypothalamus-pituitary neuroendocrine circuits, i.e., GnRH-gonadotropins and CRH-ACTH systems. These results suggested that hypothalamic CA input might affect on the activities of gonad and adrenal through modulation of hypothalamus-pituitary function, providing plausible explanation for frequent occurrence of sexual dysfunction and poor stress-response in PD patients.

• Development and Reproduction
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• v.5 no.1
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• pp.1-8
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• 2001

Golden hamsters show the reproductive activity that is determined by the photoperiod (length of light per day). Photoperiod is an environmental factor that is predictable through an entire year. The hamsters are sexually active in summer during which day length exceeds night time. The critical length is at least 12.5 hours of light in a day where reproductive function is maintained. The information of photoperiod is mediated by the pineal gland because removal of pineal gland blocks the influence of photoperiod on reproductive activity. The hamsters without pineal gland maintain sexual activity and promote it in a situation that suppresses gonadal activity. The pineal gland secretes melatonin that reflects the photoperiod. The appropriate administrations of melatonin into both pineal intact and pinealectomized hamsters lead to a gonadal reression. The results suggest that melatonin constitutes a part of control mechanism whereby environmental information is transduced to neuroendocrine signal respensible for the functional integrity of the reproductive system. Despite of the intense studies, the action site of melatonin is on the whole unknown. It is mainly due to the lack of acute efffct of melatonin on the secretion of reproductive hormones. However, sexually regressed animals display the low levelsof gonadotropins and the augmentation of the hypothalamic gonadotropin-releasing hormone (GnRH) content, implying that the antigonadotropic effects either by photoperiod and/or by the treatment of melatonin are mediated by the GnRH neuronal system. The action mechanism by which melatonin exerts its effect on GnRH neuron needs to be investigated. Recent cloning of melatonin receptor will contribute to examine various and putative potencies of melatonin via its anatomical identification and the action mechanism of melatonin on target tissues at the molecular level.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.55 no.1
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• pp.17-22
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• 2022

Successful reproduction in vertebrates necessitates complex interactions along the brain-pituitary-gonad axis, it is determined by gonadotropin releasing hormone produced in the hypothalamus of the brain, gonadotropin synthesized in the pituitary gland, and sex hormone secreted by the gonads. The goal of this study was to secure and test technology for controlling (inhibiting) sexual maturation hormones such as maturation hormones through hormone regulation. We studied the effect on sexual maturation of zebrafish Danio rerio by tamoxifen, anastrozole, exemestane and dopamine 4 kinds of sexual maturation inhibitors to feed and after administration. As a result, 4 kinds of sexual maturation inducing substances were mixed with zebrafish feed, it could be concluded that all of them were effective in inhibiting sexual maturation by reducing mRNA levels of genetic materials related to sexual maturation.

• The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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• v.12 no.2
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• pp.121-124
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• 2007

Freshwater-adapted maturing chum salmon (Oncorhynchus keta) involuntarily captured by stationary nets in Yang-yang seashore areas were transferred to freshwater in an outdoor raceway tank at Yeongdong Inland Fisheries Research Institute, NFRDI, Yang-yang, Gangwon, Korea and kept over 1 day until the start of the experiments. The freshwater-adapted females were single-injected intraperitoneally with gonadotropin-releasing hormone analogue, (GnRH-a: $70\;{\mu}g/kg$ body weight, BW) alone or combined with a dopamine receptor antagonist, pimozide($700\;{\mu}g/kg$ BW). Although gonadosomatic indices [GSI, (gonad weight/BW)${\times}100$] did not show significant changes in both 2004 and 2005, GSI of GnRH-a-injected fish during the 2005 trial slightly increased on the 5th and 7th days post-injection compared to those of vehicle treated fish. Hepatosomatic indices [HSI, (liver weight/BW)${\times}100$] of fish injected with GnRH-a alone and combined with pimozide decreased significantly on the 7th day post-injection in 2004(P<0.05). In 2005 trials, HSI was significantly reduced in GnRH-a treated fish on the 7th day post-injection (P<0.05). Pimozide-injected fish showed a pattern with increase of GSI and decrease of HSI, without significant differences. Taken together, these results suggest that at least in part hypothalamic hormones and dopamine receptor antagonist may induce sexual maturation in freshwater-adapted maturing chum salmon. It remains to evaluate these preliminary results by further researches.

• Clinical and Experimental Pediatrics
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• v.50 no.2
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• pp.198-204
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• 2007

Purpose : The hope that arresting pubertal developement might increase final adult height has led to an attempt to use GnRH agonist (GnRHa) in children with early puberty and poor growth prognosis. We investigated the growth-promoting effect of GnRH agonists with or without growth hormone (GH) in girls with early puberty and decreased predicted adult height (PAH). Methods : Thirty five girls with advanced bone age and early pubertal signs were randomized for treatment for about 1 year with monthly GnRHa in group 1 (n=18), or with a combination of GH and GnRHa in group 2 (n=17). The following growth parameters were compared between groups, and the difference ($\Delta$) before and after treatment : chronological age (CA), bone age (BA), $\Delta$(BA-CA), height (HT), target height (TH), predicted adult height (PAH), $\Delta$ (TH-PAH), serum insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein (IGFBP-3). Results : Before treatment, BA, TH, PAH Standard deviation scores (SDS), $\Delta$(TH-PAH) were not different between the two groups, but CA was higher in group 2 and $\Delta$(BA-CA) were higher in group 1 (P<0.05). After $1.06{\pm}0.93$ year of treatment, $\Delta$ (BA-CA) decreased and there were significant changes in PAH and $\Delta$ (TH-PAH), especially in group 2 (P<0.05 in group 1, and P<0.001 in group 2). In both groups, IGF-1 and IGFBP-3 were not different before and after treatment, but after treatment, IGF-1 level in group 2 was marginally higher than IGF-1 in group 1 (P<0.1). Conclusion : Compromised predicted adult height in girls with early puberty and advanced bone age was significantly improved with GnRH with/without GH treatment in the short-term period. The addition of GH to GnRHa results in a significant increase in PAH compared to GnRHa alone because GnRHa suppressed growth hormone-IGF-1 axis. For comparison of final adult height, further longitudinal follow-up will be needed.

• Clinical and Experimental Reproductive Medicine
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• v.31 no.4
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• pp.225-234
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• 2004

Objectives: To evaluate the efficacy of GnRH antagonist cetrorelix in women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) and to determine changes in serum hormone concentrations during cetrorelix administration. Methods: We performed a clinical trial on 30 patients undergoing COH with highly purified follicular stimulating hormone (HP-FSH) and gonadotropin releasing hormone antagonist (GnRHant), cetrorelix. FSH was administrated from day 2 or 3 of cycle with fixed dose and adjusted according to individual response. 0.25 mg of cetrorelix was injected daily subcutaneously from stimulation day 5 until the day of hCG administration. Daily ultrasound monitoring was performed for growing follicles and serum levels of luteinizing hormone (LH), estradiol ($E_2$) and progesterone were measured daily during cetrorelix administration. Up to 4 embryos were transferred. Results: Mean age of enrolled patients was $32.0{\pm}3.4$ years (mean $\pm$ S.D.). All of 30 patients underwent oocyte pick-up, and embryo transfer was done in 28 patients. The total and mean numbers of received oocytes were 196 and $6.5{\pm}4.7$, the number of fertilized eggs was 111, and the fertilization rate was 56.6%. Total duration of FSH administration was $9.2{\pm}2.2$ days and mean of $24.3{\pm}7.7$ ampules of HP-FSH was administered. Total duration of cetrorelix administration was $5.7{\pm}1.9$ days. Serum LH and progesterone levels were maintained in the range of $1.4{\sim}2.9\;mIU/mL$ and $0.3{\sim}0.6\;ng/mL$, which respectively reflected effective prevention of premature LH surge. Clinical pregnancies were achieved in 9 patients, and overall clinical pregnancy rate was 30.0% per oocyte retrieval, and 32.1% per embryo transfer. Conclusion: GnRH antagonist is safe and convenient for COH for IVF-ET and effective with optimal pregnancy rate.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.32 no.2
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• pp.204-210
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• 1999

The present studies were conducted to evaluate the effects of activin-A on gonadotropins (GTHs) release in testosterone-treated immature rainbow trout Oncorhpynchus mykiss. The administration of testosterone elevated pituitary level of GTH II but not of GTH I. In this study using primary cultures of dispersed pituitary cells in static incubation, dose-dependent increases in GTH II release was observed in the activin-treated group at day 3 of incubation (long-term incubation), but not at day 1 of incubation (short-term incubation). Dopamine, a potent inhibitor of gonadotropin-releasing hormone (GnRH)-stimulated GTH II release in rainbow trout, was only partially effective in decreasing actvin-induced GTH II release. Furthermore, salmon GnRH (sGnRH)-stimulated GTH II release was not potentiated by the pretreatment with activin. However, the control mechanisms of GTH I release by activin and other hormones were not observed in the all tested experiments. The results of these studies support the contention that in contrast with the usual stimulatory effects of activin on GTH release in mammals, activin exerts long-term stimulatory actions on GTH II release in rainbow trout. The control mechanism of GTH I release, however, is a question that remains to be elucidated.

• Proceedings of the Korean Society of Fisheries Technology Conference
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• 2000.05a
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• pp.300-301
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• 2000

고급단백질의 수요가 증가함에 따라 양식어류개발의 필요성이 가중되면서 유용어종을 대상으로 계획적이고 안정적인 대량종묘를 확보하기 위해서는 인위적으로 성숙/산란을 조절할 수 있는 방법을 개발하는 것이 우선 과제이다. 이러한 방법에는 적합한 호르몬제를 사용하던지 또는 사육 환경조건을 변화시키는 방법 등이 있는데(Donaldson and Hunter, 1983) 호르몬제를 사용할 경우, 자연산란과 비교해볼 때 난질이 좋지않아 수정률 저하를 초래할 경우가 많다. 지금까지 양식현장에서는 HCG(태반선성선자극호르몬)가 널리 사용되어왔으나, 최근에는 GnRH (gonadotropin hormone-releasing hormone)를 이용한 성숙/배란유도가 성행되고 있으며 이에 대한 투여방법도 및 가지로 연구되고 있다 (Okumura and Sakae, 1993; Leu and Chou, 1996). (중략)

• The Journal of Pediatrics of Korean Medicine
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• v.36 no.3
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• pp.1-18
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• 2022

Objectives The purpose of this study was to investigate the current status of interventional clinical trial registration for children with precocious puberty and to secure basic data for the design of clinical trials for traditional Korean medicine treatment of precocious puberty. Methods The following resources were used to search for data: Clinicaltrial.gov, World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), and Clinical Research Information Service (CRIS), using the search terms, 'Precocious puberty', 'child'. All clinical trials which were registered as of June 2022 were used. Results For the intervention and clinical trial design, gonadotropin releasing hormone (GnRH) analog was reported in 41.7% of trials, and single group assignment was performed in 66.7% of the studies. Prior consent had not been reported in 50% of the studies. Tanner stage and GnRH stimulation tests were reported by multiple trials as inclusion criteria, and prior treatment experiences for trial drugs were reported as exclusion criteria. The peak serum concentration of luteinizing hormone following GnRH stimulation test was used as a primary outcome in 45.8% of clinical trials, and other growth-related indicators such as growth rate, height, and predicted adult height were also reported. Conclusions In consideration of the design, eligibility criteria, and outcome measurement of the existing clinical trials identified in this study, it should be referred to in the design of clinical trials for traditional Korean medicine treatment of precocious puberty.