중추성 성조숙증 및 조기 사춘기 여아에서 성선자극호르몬 방출호르몬작용제의 용량에 따른 사춘기 억제 효과 비교

심계식,배종우,양유정 대한소아청소년과학회 2008 Clinical and Experimental Pediatrics (CEP) Vol.51 No.6

Purpose:There has been considerable disagreement regarding the most appropriate dosage of gonadotropin-releasing hormone agonist in cases of central precocious puberty. The aim of this study was to determine the appropriate dosage for suppression of the puberty in girls with central precocious or early puberty. Methods:Twenty-two girls with early puberty were randomly subjected to 3 types of dosages of leuprolide acetate for at least 6 months. The number of cases in groups 1, 2, and 3 were 7, 7, and 8, and dosages were 70, 90, and 110 µg/ kg/-month, respectively. Height, weight, bone age, Tanner stage of breast development, and serum levels of LH, FSH, estradiol, and progesterone were measured before treatment and after 6 months of treatment. The number of cases of puberty suppression was compared using a modified puberty suppression score with a nonparametric chi-square test. Results:There were no significant differences of chronologic and bone ages among the groups. There was a significant decrease in height SDS gain after 6 months in group 3 (P<0.05) compared with groups 1 and 2. Serum levels of LH, FSH, estradiol and progesterone were all significantly decreased after treatment in all 3 groups (P<0.05). The number of cases of puberty suppression in each group were 4 (57%), 5 (71%), and 8 (100%). There was a significantly increased proportion of suppression of puberty in group 3 (P<0.05). Conclusion:It was necessary to use a higher dose of gonadotropin-releasing hormone agonist to suppress early puberty in girls; however further longitudinal study will be needed for their prognosis of final adult height. (Korean J Pediatr 2008;51:635-639) Purpose:There has been considerable disagreement regarding the most appropriate dosage of gonadotropin-releasing hormone agonist in cases of central precocious puberty. The aim of this study was to determine the appropriate dosage for suppression of the puberty in girls with central precocious or early puberty. Methods:Twenty-two girls with early puberty were randomly subjected to 3 types of dosages of leuprolide acetate for at least 6 months. The number of cases in groups 1, 2, and 3 were 7, 7, and 8, and dosages were 70, 90, and 110 µg/ kg/-month, respectively. Height, weight, bone age, Tanner stage of breast development, and serum levels of LH, FSH, estradiol, and progesterone were measured before treatment and after 6 months of treatment. The number of cases of puberty suppression was compared using a modified puberty suppression score with a nonparametric chi-square test. Results:There were no significant differences of chronologic and bone ages among the groups. There was a significant decrease in height SDS gain after 6 months in group 3 (P<0.05) compared with groups 1 and 2. Serum levels of LH, FSH, estradiol and progesterone were all significantly decreased after treatment in all 3 groups (P<0.05). The number of cases of puberty suppression in each group were 4 (57%), 5 (71%), and 8 (100%). There was a significantly increased proportion of suppression of puberty in group 3 (P<0.05). Conclusion:It was necessary to use a higher dose of gonadotropin-releasing hormone agonist to suppress early puberty in girls; however further longitudinal study will be needed for their prognosis of final adult height. (Korean J Pediatr 2008;51:635-639)

Effects of gonadotropin-releasing hormone agonist treatment on final adult height in boys with idiopathic central precocious puberty

Cho Ah Young,Ko Su Yeong,Lee Jae Hee,Kim Eun Young 대한소아내분비학회 2021 Annals of Pediatirc Endocrinology & Metabolism Vol.26 No.4

Purpose: There are few reports on the therapeutic effects of gonadotropin-releasing hormone agonists in boys with central precocious puberty, and studies reported in Korea are very rare. We aimed to assess the significance of clinical factors and the effects of gonadotropin-releasing hormone agonist treatment on final adult height in boys diagnosed with central precocious puberty.Methods: We retrospectively evaluated the medical records of 18 boys treated for idiopathic central precocious puberty between 2007 and 2018 at Chosun University Hospital. Gestational age, birth weight, and parental height were assessed at the initial visit. Chronological age, bone age, bone age/chronological age ratio, height and height standard deviation scores, predicted adult height, body mass index, and hormone levels were assessed during the treatment period.Results: At the time of diagnosis, the chronological age was 9.9±0.6 years, the bone age was 11.6±1.0 years, and the bone age/chronological age ratio was 1.20±0.1. The bone age/chronological age ratio decreased significantly to 1.12±0.1 at the end of treatment (P<0.05). The luteinizing hormone/follicular stimulating hormone ratios were 3.4±1.2, 0.6±0.4, and 0.6±1.0 at the start of treatment, after 1 year of treatment, and at the end of treatment, respectively. After gonadotropin-releasing hormone agonist treatment, the final adult height reached 172.0±4.8 cm compared to the target height range of 171.0±4.0 cm.Conclusion: In boys with central precocious puberty, gonadotropin-releasing hormone agonist treatment improved growth potential.

Gonadotropin-releasing Hormone Agonist Plus Aromatase Inhibitor in the Treatment of Uterine Leiomyoma in Near Menopause Patient: A Case Series Study

( Sanam Moradan ) 대한폐경학회 2018 대한폐경학회지 Vol.24 No.1

Objectives: There are many drugs for of symptomatic fibroids. Gonadotropin-releasing hormone (GnRH) agonists are the well known drugs. Also, aromatase inhibitors are effective. All published studies surveyed the effect of one of these two drugs. In this study as the first study decided to evaluate the effectiveness of the combination of GnRH agonists + aromatise inhibitor on the uterine fibroids. Methods: A cross-sectional prospective case series study was performed on 10 known cases of uterine fibroids late perimenopause, at least 3 myomas >5 cm, abnormal uterine bleeding and anemia due to fibroids, candidate for hysterectomy, no tendency to surgery. A single dose of Diphereline 11.25 mg, SR plus 2.5 mg of Letrozole daily for 4 weeks with add-back therapy + calcium carbonate were used. The second dose of Diphereline 11.25 mg, SR was used 3 months after the first injection. The patients were followed until 3 years. Results: The mean age of the study group was 49.90 ± 1.66. The mean fibroid size reduced from 15.05 ± 57.20 cm to 13.56 ± 39.39 cm (P = 0.012) and fibroid volume reduced from 72.78 ± 110.6 to 50.96 ± 64.2 (P = 0.116). There was no signification changes in the serum level of hormones at the end of six months. Eight cases were menopause at the end of the study and hypoestrogenism symptoms did not happened in none of the cases until the end of 24 months. Except in one case, there was no need to do surgery on others. Conclusions: Combination of Diphereline + Letrozole probably could prevent surgery in cases that have multiple fibroids, perimenopause, anemic and candidate for surgery. (J Menopausal Med 2018;24:62-66)

성조숙증으로 진단된 여아에서 성선자극호르몬 방출호르몬 효능약제 치료 후 첫 3개월 성장속도가 1년 후 성장에 미치는 영향

신정희,허원경,황일태,양승 대한소아내분비학회 2011 Annals of Pediatirc Endocrinology & Metabolism Vol.16 No.2

Purpose:The aim of this study was to assess the usefulness of growth velocity at 3 months after gonadotropin- releasing hormone (GnRH) agonist treatment as a predictive value of 1 year growth velocity after treatment in girls with precocious puberty. Methods: We studied 30 Korean girls with precocious puberty whose chronologic and bone age were less than 9 years and 11 years old, respectively at diagnosis. They treated with a 4 week interval GnRH agonist subcutaneous injections for at least more than 1 year. The patients who were treated with growth hormone simultaneously excluded for this study. Data were collected from chart review retrospectively. We measured heights and calculated growth velocities of the subjects at 3 months and 1 year after GnRH agonist treatment. Results: The mean chronologic age and bone age of the subjects were 8.3±0.8 year and 10.4±0.6 years, respectively. The growth velocity at 3 months, 6 months, 9 months and 1 year after GnRH agonist treatment were 7.1±2.6, 6.6±2.1, 5.7±1.3 and 5.8±0.9 cm/yr, respectively. The positive correlation between the growth velocity at 3 months and 6 months, 9 months, 1 year after GnRH agonist treatment were shown(P ˂0.001, P ˂0.001, P =0.002, respectively). Conclusion: In this study, the growth velocity at 1 year after GnRH agonist treatment may be predicted by the growth velocity at 3 months after treatment. The patient whose growth velocity at 3 months after GnRH agnoist treatment was low would be needed to observe the growth pattern carefully and to consider combined growth hormone treatment, if needed. It may be deserve further studies to improve final height in patients with central precocious puberty in various conditions.(J Korean Soc Pediatr Endocrinol 2011;16:80-85) 목 적:진성 성조숙증의 치료에 있어서 성선자극호르몬 방출호르몬 효능약제 (GnRH agonist)의 사용은 사춘기의 진행과 골성숙을 억제하여 최종 성인신장을 향상시킨다고 알려져 있다. 그러나 GnRH agonist의 투여 효과는 대상군에 따라 다양한 결과를 보인다. 또한 GnRH agonist 단독 치료 및 성장호르몬의 병용 치료를 비교했을 때 성장호르몬 병용투여가 골연령의 증가없이 예측 성인신장을 향상시킨다고 보고하였다. 따라서 본 연구에서는 진성 성조숙증 여아에서 GnRH agonist 치료 3개월 후의 성장속도로 치료 1년 후의 성장속도를 예측할 수 있는 지를 알아보고 이를 통해 성장호르몬의 병용 여부를 치료 초기에 결정할 수 있는 지를 확인하고자 하였다. 방 법:한림대학교 강동성심병원 소아청소년과에서 진성 성조숙증으로 진단받은 여아 중 진단 당시 연령이 9세 미만, 골연령이 11세 이하, 최소 1년간 성선자극호르몬 방출호르몬 효능약제(GnRH agonist)를 4주 간격으로 치료받았던 30명을 연구 대상에 포함시켰다. 성장호르몬을 병용투여한 환아는 대상에서 제외하였다. 자료수집은 외래차트를 통하여 이루어졌고 성장속도는 치료 3개월 후, 6개월 후, 9개월 후, 1년 후의 신장을 각각 연성장속도로 재계산하여 비교하였다. 결 과:대상 환아의 평균 연령은 8.3±0.8세, 평균 골연령은 10.4±0.6세였다. GnRH agonist 치료 3개월 후 평균 성장속도는 7.1±2.6 cm/년, 치료 1년 후 평균 성장속도는 5.8±0.9 cm/년이었다. GnRH agonist 치료 3개월 후 성장속도와 치료 1년 후 성장속도는 의미있는 양의 상관관계를 보였다(r=0.553, P=0.002). 결 론:본 연구에서 성선자극호르몬 방출호르몬 효능약제 치료 3개월 후의 성장속도가 1년 후의 성장속도와 양의 상관관계를 보이며 추후 장기적인 성장 평가 및 최종 성인신장과의 연관성 등에 대한 추가적인 연구가 필요할 것으로 생각된다.

Effects of human growth hormone on gonadotropin-releasing hormone neurons in mice

Bhattarai, Janardhan P.,Kim, Shin-Hye,Han, Seong-Kyu,Park, Mi-Jung The Korean Pediatric Society 2010 Clinical and Experimental Pediatrics (CEP) Vol.53 No.9

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.

Effects of various photoperiods on Kisspeptin and reproductive hormones in the goldfish, Carassius auratus

신현숙,최철영,송진아,최지용,김나나,최영재,성시내,박미선,민병화 한국통합생물학회 2014 Animal cells and systems Vol.18 No.2

The study aimed to test differences in the hormones of the hypothalamus–pituitary–gonad axis, Kisspeptin (Kiss) and sexsteroids, and the sexual maturation of goldfish (Carassius auratus) according to various photoperiods: 10 h light (L):14 hdark (D) (short day), 12L:12D (control), and 14L:10D (long day). To investigate the sexual maturation under variousphotoperiods, quantitative real-time PCR (QPCR) assays for salmon gonadotropin-releasing hormone, chicken gonadotropinreleasinghormone, gonadotropin hormones (GTHs), Kisspeptin 1 (Kiss1), and its receptor, G protein-coupled receptor 54(GPR54), were developed. mRNA expression was monitored in cultured pituitary cells (in vitro) of various photoperiodgroups. Furthermore, we injected or treated the animals with Kiss and found that Kiss treatment increases the mRNAexpression levels of GTHs. We measured the plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), and17α-hydroxypregnenolone levels. The gonadotropin-releasing hormones (GnRHs), GTHs, Kiss1/GPR54 mRNA expression,plasma FSH, LH, and 17α-hydroxypregnenolone levels in the 14L:10D group were significantly higher than in theother groups. These results suggest that light length regulates sex maturation by GnRH and Kiss1 in the brain of the goldfish.

Gonadotropins Regulate the mRNA Expression of Gonadotropin-Releasing Hormone and Its Receptors in the Mouse Ovary and Uterus

문소은,석은지,하진아,양현원,윤보경,이민주 한국발생생물학회 2024 발생과 생식 Vol.28 No.1

Gonadotropin-releasing hormone (GnRH), a critical hormone produced in the hypothalamus, is essential for regulating reproductive processes. It has also been demonstrated the presence of GnRH and its receptors (GnRHR) in ovarian and uterine tissues, but little was known about the regulation mechanism of their expression in these organs and ovarian aging. Therefore, the aim of this study was to investigate the expression of GnRHR in the ovary and uterus of mice, particularly after high-dose gonadotropin treatments and in relation to aging. Quantitative realtime-PCR (qRT-PCR) revealed that pituitary gland had the highest GnRHR expression in both young and aged mice. In addition, liver expression was higher in young mice, whereas thymus expression was higher in aged mice. GnRHR mRNA was present in the ovaries of both young and aged mice but nearly undetectable in the uterus of aged mice. We next examined the expression of GnRHR in the ovary and uterus in response to high-dose administration of pregnant mare serum gonadotropin (PMSG). After PMSG administration, GnRH mRNA levels were significantly decreased in the ovary but increased in the uterus. The expression of GnRH mRNA in these organs showed opposite trends to that of GnRHR expression. These results suggest the involvement of GnRH in age-related reproductive decline and the potential effects of high-dose gonadotropin treatments on reproductive organ function.

Uterine fibroid shrinkage after short-term use of selective progesterone receptor modulator or gonadotropin-releasing hormone agonist

( Min Jin Lee ),( Bo Seong Yun ),( Seok Ju Seong ),( Mi-la Kim ),( Yong Wook Jung ),( Mi Kyoung Kim ),( Hyo Sook Bae ),( Da Hee Kim ),( Ji Young Hwang ) 대한산부인과학회 2017 Obstetrics & Gynecology Science Vol.60 No.1

Objective The aim of this study was to evaluate the effect of short-term use of selective progesterone receptor modulator (SPRM) or gonadotropin-releasing hormone (GnRH) agonist on uterine fibroid shrinkage among Korean women. Methods This retrospective study involved 101 women with symptomatic uterine fibroids who received ulipristal acetate (SPRM, n=51) and leuprolide acetate (GnRH agonist, n=50) for 3 months between November 2013 and February 2015. The fibroid volume was measured both before and after treatment using ultrasonography, computed tomography, and magnetic resonance imaging. The outcomes were compared between the SPRM and GnRH agonist groups. Results The median rate of fibroid volume reduction after SPRM treatment was 12.4% (IQR -14.5% to 40.5%) which was significantly lower than the reduction rate observed after GnRH agonist treatment (median 34.9%, IQR 14.7% to 48.6%, P=0.004). 19 of 51 (37.3%) patients with SPRM treatment did not show any response of volume shrinkage, while 7 of 50 (14.0%) women with GnRH agonist showed no response (P=0.007). Conclusion Short-term SPRM treatment yields lower volume reduction than GnRH agonist treatment in Korean women with symptomatic fibroids. Further large-scale randomized trials are needed to confirm our findings.

진성 성조숙증 여아에서 Gonadotropin-Releasing Hormone Agonist 치료 중 성장속도에 따른 임상 인자들의 비교

남효경,신정연,오연정,이영준,유영,박상희,이기형 대한내분비학회 2010 Endocrinology and metabolism Vol.25 No.3

Background: The aim of this study was to investigate the favorable factors for gonadotropin-releasing hormone (GnRH) agonist treatment with regard to the growth velocity and the predicted adult height (PAH) in central precocious puberty (CPP) girls. Methods: We reviewed the clinical and auxological parameters in 46 CPP girls who were treated with GnRH agonist at the pediatric endocrinology clinic of Korea University Hospital from January 2001 to August 2007. We divided the two groups according to the growth velocity of 5 cm/yr and we assessed the related factors associated with growth velocity. We also assessed the changes in PAH for two years. Results: The pretreatment chronological age and bone age were significantly younger in the high growth velocity group (> 5 cm/yr)compared to that of the low growth velocity group (7.8 ± 0.9 year vs. 8.4 ± 0.5 year, 9.4 ± 1.2 year vs. 10.1 ± 0.9 year, respectively) (P <0.05). The PAH after treatment was significantly greater in the high growth velocity group (> 5 cm/yr)(P < 0.05). Growth velocity during treatment had negative correlation with the pretreatment chronological age and positive correlation with the PAH after one and two years of treatment (r = -0.45, P < 0.05 and r = 0.51, P < 0.01). PAH had positive correlation with the treatment duration (r = 0.31, P < 0.05). Conclusion: In our study, the growth velocity during GnRH agonist treatment was negatively related to age at the initiation of treatment. Therefore, earlier treatment is important to improve the outcomes and to maintain appropriate growth velocity in CPP girls.

Immunocontraceptive Effects in Male Rats Vaccinated with Gonadotropin-Releasing Hormone-I and -II Protein Complex

( Yong-hyun Kim ),( Byung-joo Park ),( Hee-seop Ahn ),( Sang-hoon Han ),( Hyeon-jeong Go ),( Joong-bok Lee ),( Seung-yong Park ),( Chang-seon Song ),( Sang-won Lee ),( In-soo Choi ) 한국미생물생명공학회(구 한국산업미생물학회) 2019 Journal of microbiology and biotechnology Vol.29 No.4

Immunocontraception has been suggested as an optimal alternative to surgical contraception in animal species. Many immunocontraceptive vaccines have been designed to artificially produce antibodies against gonadotropin-releasing hormone-I (GnRH-I) which remove GnRH-I from the vaccinated animals. A deficiency of GnRH-I thereafter leads to a lack of gonadotropins, resulting in immunocontraception. In this study, we initially developed three immunocontraceptive vaccines composed of GnRH-I, GnRH-II, and a GnRH-I and -II (GnRH-I+ II) complex, conjugated to the external domain of Salmonella Typhimurium flagellin. As the GnRH-I+II vaccine induced significantly (p < 0.01) higher levels of anti-GnRH-I antibodies than the other two vaccines, we further evaluated its immunocontraceptive effects in male rats. Mean testis weight in rats (n = 6) inoculated twice with the GnRH-I+II vaccine at 2-week intervals was significantly (p < 0.01) lower than in negative control rats at 10 weeks of age. Among the six vaccinated rats, two were non-responders whose testes were not significantly reduced when compared to those of negative control rats. Significantly smaller testis weight (p < 0.001), higher anti-GnRH-I antibody levels (p < 0.001), and lower testosterone levels (p < 0.001) were seen in the remaining four responders compared to the negative control rats at the end of the experiments. Furthermore, seminiferous tubule atrophy and spermatogenesis arrest were found in the testis tissues of responders. Therefore, the newly developed GnRH-I+ II vaccine efficiently induced immunocontraception in male rats. This vaccine can potentially also be applied for birth control in other animal species.