• Development and Reproduction
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• v.10 no.4
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• pp.215-225
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• 2006

Precocious puberty is defined as the appearance of secondary sex characteristics before age 8 years in girls (or menarche before age 9 years) and before 9 years in boys. The age of onset of puberty is progressing to younger age. The pubertal activation of gonadotrophin releasing hormone(GnRH) release requires coordinated changes in excitatory or inhibitory amino acids, growth factors, and a group of transcriptional regulators. A number of factors affecting precocious puberty were explored, including the role of genetic factors, nutrition(body fat) and exposure to endocrine disrupting chemicals. In addition to the psychosocial disturbances associated with precocious puberty, the premature pubertal growth spurt and the accelerated bone maturation result in reduced adult height. Precocious puberty may be gonadotrophin-dependent premature activation of the GnRH pulse generator or gonadotrophin-independent. In rapidly progressing central precocious puberty, GnRH agonists appear to increase final height. However more data on the effect and long-term safety of GnRHa are needed.

• Development and Reproduction
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• v.4 no.1
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• pp.109-114
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• 2000

The present study was undertaken to examine the effects of ethanol on the ovarian steroidogenic acute regulatory protein(StAR) gene expression during prepubertal and onset of puberty. From day 25, each rat began receiving either a control saline or ethanol. Animals were sacrificed on day 27 and 32, and their ovaries and blood were collected. In the present results, ethanol treatment significantly decreased serum luteinizing hormone contents at both time points. Uterine weights of ethanol-treated group were significantly lighter than control group at early time point while there was no noticeable discrepancy at late time point. Vaginal openings, a marker of onset of puberty, also clearly delayed in ethanol-treated group. Using an in situ hybridization histochemistry, we determined the expression of mRNAs encoding StAR. Ovaries from ethanol-treated rats showed a suppresed expression of StAR mRNA. These results demonstrate that ethanol can disturb the prepubertal ovarian function and onset of puberty, at least in part, through the inhibition of ovarian StAR gene expression.

• Development and Reproduction
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• v.11 no.3
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• pp.245-251
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• 2007

Vinclozolin(VCZ), a systemic dicarboximide fungicide, has been used in the control of diseases caused by microorganism of some species in fruits, vegatables and ornamental plants. Although VCZ itself is a very weak antagonist for androgen receptor binding, both melabolites M1 and M2 are effective antagonists. The present study was undertaken to examine whether prepubertal exposure to VCZ affects on the onset of puberty and the associated reproductive parameters such as hormone receptor expressions in female rats. VCZ(10 mg/kg/day) was administered daily from postnatal day 21(PND 21) through the day when the first vaginal opening(V.O.) was observed. Gross anatomy and weight of reproductive tissues were compared to test the VCZ's effects on the cell proliferation. Furthermore, histological studies were performed to assess the structural alterations in the tissues. To determine the transcriptional changes in progesterone receptor(PR), total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction(RT-PCR). As a result, delayed V.O. was shown in the VCZ group(PND $34.00{\pm}1.22$) compared to the control group(PND $38.20{\pm}1.92$; p<0.01). VCZ treatment significantly decreased the wet weight of ovaries and uteri compared to the control group(p<0.01). Graafian follicles and corpora lutea were observed only in the ovaries from the control animals, while numerous primary, secondary follicles and small atretic follicles were observed in the ovaries from VCZ group. Similarly, hypotrophy of luminal and glandular uterine epithelium was found in the VCZ group. In the semi-quantitative RT-PCR studies, the transcriptional activity of PR in ovary(p<0.01) from VCZ group were significantly lower than those from the control group while in uterus were similar compared with the control group. The present studies demonstrated that the acute exposure to VCZ during the critical period of prepubertal stage could inactivate the reproductive system resulting delayed puberty in female rats.

• Development and Reproduction
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• v.10 no.4
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• pp.255-261
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• 2006

Although some phytoes rogens might have beneficiary rather than adverse effects, most endocrine disrupting compounds(EDCs) are considered to be harmful to human and wildlife health through interfering the endocrine system. Previously we found that prepubertal exposure to genistein(GS), a well-known isoflavone phytoestrogen, could activate the reproductive system of immature female rats resulting precocious puberty. Interestingly, di(2-ethyl hexyl) phthalate(DEHP) exposure brought inverse result, a delayed puberty, in the same experimental regimen. In this study, we examined whether prepubertal exposure to GS or DEHP affect the gene expressions of estrogen receptors($ER\;{\alpha}$ and $ER\;{\beta}$) and LH receptor(LHR) which represent the maturational status of ovary and uterus in immature rats. GS (100 mg/kg/day) was administered daily from postnatal day 25 to the day when the first vaginal opening(VO) was observed, and the animals were sacrificed on the next day(day 32). Similarly, DEHP(l00 mg/kg/day) was administered daily from postnatal day 25 through the day when the first V.O. in control group was observed, and the animals were sacrificed on the next day(day 36). To determine the transcriptional changes in the hormone receptors, total RNAs were extracted from ovary and uterus and were applied to semi-quantitative reverse transcription polymerase chain reaction(RT-PCR). In the GS group, the transcriptional activities of $ER\;{\alpha}$, $ER\;{\beta}$ and LHR in uterus and LHR in ovary were significantly increased when compared to those of control group. In the DEHP group, the transcriptional activities of all the hormone receptors measured were significantly lowered when compared to those of control group. These alteration of the reproductive hormone receptor expressions in ovary and uterus might be represent the phenotypic aspects(secondary sexual characteristics) such as tissue weights and reproductive hormone levels during perinatal period in immature female rats.

• Development and Reproduction
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• v.10 no.2
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• pp.147-154
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• 2006

Phthalates such as di(2-ethyl hexyl)phthalate(DEHP) are industrial chemicals with wide-ranging human exposures because of their use in plastics and other common consumer products. Consequently, their adverse effects as endocrine disruptor in the reproductive physiology of both laboratory rodents and human have been studied extensively. The present study was undertaken to examine whether prepubertal exposure to DEHP affects on the onset of puberty and the associated reproductive parameters such as hormone receptor expressions in female rats. DEHP(100mg/kg/day) was administered daily from postnatal day 25(PND 25) through the day when the first vaginal opening(VO) was observed, and the animals were sacrificed on the next day. Gross anatomy and weight of reproductive tissues were compared to test the DEHP's effects on the cell proliferation. Furthermore, histological studies were performed to assess the structural alterations in the tissues. Specific radioimmunoassay was carried out to measure serum LH levels. To determine the transcriptional changes in progesterone receptor(PR), total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction(RT-PCR). As a result, delayed VO was shown in the DEHP group(PND $37.3{\pm}0.7$) compared to the control group(PND $35.3{\pm}0.7$; p<0.05). DEHP treatment significantly decreased the wet weight of ovaries and uteri compared to the control group(p<0.05). Interestingly, elevation of serum LH levels was shown in the DEHP group(p<0.05). Graafian follicles and corpora lutea were observed only in the ovaries from the control animals. Numerous primary, secondary follicles and small atretic follicles were observed in the ovaries from DEHP-treated animals. Similarly, hypotrophy of luminal and glandular uterine epithelium was found in the DEHP-treated group. These effects were probably due to the inhibitory effects of DEHP on the synthesis and secretion of estrogen from granulosa cells. In the semiquantitative RT-PCR studies, the transcriptional activities of PR in both ovary(p<0.05) and uterus(p<0.01) from DEHP-treated animals were significantly lower than those from the control animals. The present studies demonstrated that the acute exposure to DEHP during the critical period of prepubertal stage could inactivate the reproductive system resulting delayed puberty in female rats.

• Clinical and Experimental Pediatrics
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• v.46 no.8
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• pp.803-810
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• 2003

Purpose : The purpose of this study was to evaluate the factors affecting the final adult height and total height gain in idiopathic and organic growth hormone deficient(GHD) children after growth hormone(GH) treatment. Methods : Thirteen patients with idiopathic GHD and 22 patients with organic GHD who had been treated with GH and attained adult final height were included in this study. Factors which could affect the final adult height(FAH) and total height gain, were evaluated. Results : Height SDS(standard deviation score) at initial GH treatment in idiopathic GHD was significantly shorter than that in organic GHD($-4.13{\pm}1.28$ vs $-1.66{\pm}1.06$, P<0.001). Growth velocity during the first year of GH treatment was $9.69{\pm}3.19cm$(idiopathic GHD) and $7.87{\pm}3.65cm$(organic GHD). Height(SDS) at puberty in organic GHD was significantly greater than in idiopathic GHD ($-0.55{\pm}1.25$ vs $-2.28{\pm}0.95$, P<0.001). Final adult height(SDS) was significantly greater in organic GHD than in idiopathic GHD($0.22{\pm}1.06$ vs $-1.44{\pm}0.84$, P<0.001). In idiopathic GHD, total height gain (SDS) was most significantly correlated with midparental height minus initial height(MPH-IH)(SDS) (r=0.886, P<0.001). Total height gain(SDS) was more significantly correlated with MPH-IH(SDS) and prepubertal height gain(SDS) in idiopathic GHD(r=0.640, P=0.01, r=0.801, P<0.001). Conclusion : Final adult height was greater in organic GHD than in idiopathic GHD patients. While total height gain(SDS) was more pronounced in children with lower initial height compared to MPH, absolute final adult height was influenced by height at puberty. To improve the final adult height in children with GHD, height at onset of puberty must be increased by early diagnosis and continuous treatment with optimal doses of GH. There results should be evaluated with more patients.

• Journal of the korean academy of Pediatric Dentistry
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• v.46 no.2
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• pp.209-218
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• 2019

This study was aimed to evaluate orofacial morphologies on the cases of developmental disorders of maxillary first molars. Panoramic radiographs, lateral cephalographs, and clinical photos of 2983 children who attended the Pediatric Dental Clinic of Pusan National University Dental Hospital from 2006 to August 2017 were assessed retrospectively. 34 patients were selected whose maxillary first molars were missed or developmentally delayed unilaterally or bilaterally. Demirjian's method was used for estimating dental age, then which was compared to chronologic age of children. Parameters expressing skeletal and dentoalveolar disharmony were checked and compared with control. Additionally, occlusion relationship was evaluated. Maxillary dental age was significantly delayed compared to chronologic age. Several parameters which show skeletal open-bite tendency and skeletal class III malocclusion with maxillary retrusion were statistically significant. Anterior crossbite and edge-bite were expected in most of these cases, but compensation by occlusion and soft tissue was also verified which might mask skeletal class III tendency. Congenital missed or developmentally delayed maxillary first molars might be related with declined growth of maxilla. If developmental disorders of maxillary first molars were verified during clinical examination, careful monitoring of orofacial growth was necessary during puberty and timed orthopedic and orthodontic intervention were considered.

• Development and Reproduction
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• v.12 no.1
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• pp.97-105
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• 2008

Vinclozolin (VCZ) is a systemic fungicide commonly used in fruits, vegetables and the wine industry. VCZ and its metabolites, butenoic acid (M1) and enanilide (M2) derivatives, act as anti-androgens through actions on the androgen receptor. Although there is growing body of evidence that VCZ's action as an endocrine disrupting chemical (EDC) in male reproductive physiology and pathphysiology, no evidence on the VCZ's EDC action in female is available yet. Previously we found that the prepubertal VCZ exposures could effectively delay the onset of puberty in female rats, suggesting the postponed or weakened activities of hypothalamus-pituitary-ovary (H-P-O) reproductive hormonal axis. The present study was performed to examine whether the VCZ administration affects the transcriptional activities of reproductive hormone-related genes in the same animal model. VCZ (10 mg/kg/day) was administered daily from postnatal day 21 (PND 21) through the day when the first vaginal opening (V.O.) was observed. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus and pituitary, total RNAs were extracted and applied to the semiquantitative reverse transcription polymerase chain reaction (RT-PCR). As a result, treatment with VCZ significantly lowered the transcriptional activity of nitric oxide synthase-2 (NOS-2) which is known to adjust gonadotropin-releasing hormone (GnRH) secretion in the hypothalamus (p<0.01). Similarly, the mRNA levels of KiSS-1, G protein-coupled receptor 54 (GPR54) and GnRH were significantly decreased in hypothalamus (p<0.01) from VCZ-treated group. As expected, the transcriptional activities of luteinizing hormone-${\beta}$ (LH-${\beta}$) and follicle stimulating hormone-${\beta}$ (FSH-${\beta}$) in the anterior pituitary from VCZ-treated group were also significantly lower than those from the control group. The present study indicates that(i) the inhibitory effect of VCZ exposure on the onset of puberty in immature female rats could be derived from the reduced transcriptional activities of gonadotropin subunits and their upstream modulators such as GnRH and KiSS-1 in hypothalamus-pituitary neuroendocrine axis, and (ii) these inhibitory effects could be mediated by NO signaling pathway.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.4 no.1
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• pp.63-70
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• 2001

Purpose: The aim of this study is to evaluate the effective role of living-related liver transplantation (LRLT) on posttransplant linear growth in children. Methods: Thirty six children were enrolled who received LRLT at Asan Medical Center from December, 1994 to February, 1999 and showed more than one-year postoperative survival. Mean height standard deviation score (zH) was analyzed according to medical records including heights during pretransplant and posttransplant follow-up periods. Results: zH of total children showed significant linear growth after LRLT from -1.58 to 0.33 at 24 posttransplant month (p<0.05). zH in children under 6 years of age, to exclude the effect of adolescent linear growth spurt, showed increment in height (p<0.05). Linear growth of children with liver cirrhosis improved and that with fulminant hepatitis was matained same. While stunted children (mean zH=-2.30) achieved good catch-up growth after transplantation, children with normal growth remained same. Children with significant hepatic dysfunction after LRLT such as chronic rejection or posttransplant lymphoproliferative disorder showed retarded posttrasplant linear growth. There was no statistical difference according to the type of immunosuppressants. Conclusion: LRLT resulted in adequate or catch-up linear growth in children with acute, chronic and metabolic liver disease. Successful LRLT suggested to be a promising option not only in long term survival but also in normal linear growth.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.3
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• pp.103-108
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• 2017

Kabuki syndrome is a rare congenital disorder that causes multiple birth defects and mental retardation. Mutation of the lysine methyltransferase 2D (KMT2D) gene is the primary cause of Kabuki syndrome. We report a 4-year-old Korean girl diagnosed with Kabuki syndrome based on distinctive facial features (eversion of the lower lateral eyelid, arched eyebrows, depressed nasal tip, prominent ears), skeletal anomalies, short stature, and molecular analysis, which revealed a novel frameshift mutation in the KMT2D gene. A 4-year-old patient had a past history of congenital cardiac malformations (coarctation of the aorta, ventricular septal defect, atrial septal defect, patent ductus arteriosus), subclinical hypothyroidism and dysmorphic features at birth including webbed neck, short fingers, high arched palate, micrognathia and horseshoe kidney. She showed unique facial features such as a long palpebral fissure, long eyelashes, arched eyebrows with sparseness of the lateral third, broad nasal root, anteverted ears, and small mouth. Her facial features suggested Kabuki syndrome, and genetic analysis discovered a novel heterozygous frameshift mutation (c.4379dup, p.Leu1461Thrfs*30) in exon 15 of the KMT2D gene. The diagnosis of our 4-year-old patient was made through thorough physical examination and history taking, and genetic testing. It is challenging to diagnose patients with Kabuki syndrome at birth, since the characteristic facial features are expressed gradually during growth. Clinical suspicion aroused by regular follow-ups may lead to earlier diagnosis and interventions.