• Asian-Australasian Journal of Animal Sciences
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• v.28 no.11
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• pp.1573-1582
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• 2015

This study was to investigate the effect of soyabean isoflavones (SIF) on onset of puberty, serum hormone concentration, and gene expression in hypothalamus, pituitary and ovary of female Bama miniature pigs. Fifty five, 35-days old pigs were randomly assigned into 5 treatment groups consisting of 11 pigs per treatment. Results showed that dietary supplementation of varying dosage (0, 250, 500, and 1,250 mg/kg) of SIF induced puberty delay of the pigs with the age of puberty of pigs fed basal diet supplemented with 1,250 mg/kg SIF was significantly higher (p<0.05) compared to control. Supplementation of SIF or estradiol valerate (EV) reduced (p<0.05) serum gonadotrophin releasing hormone and luteinizing hormone concentration, but increased follicle-stimulating hormone concentration in pigs at 4 months of age. The expression of KiSS-1 metastasis-suppressor (KISS1), steroidogenic acute regulatory protein (StAR) and 3-beta-hydroxysteroid dehydrogenase/delta-5-delta-4 isomerase ($3{\beta}-HSD$) was reduced (p<0.01) in SIF-supplemented groups. Expression of gonadotropin-releasing hormone receptor in the pituitary of miniature pigs was reduced (p<0.05) compared to the control when exposed to 250, 1,250 mg/kg SIF and EV. Pigs on 250 mg/kg SIF and EV also showed reduced (p<0.05) expression of cytochrome P450 19A1 compared to the control. Our results indicated that dietary supplementation of SIF induced puberty delay, which may be due to down-regulation of key genes that play vital roles in the synthesis of steroid hormones.

• Journal of Animal Reproduction and Biotechnology
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• v.36 no.1
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• pp.25-34
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• 2021

Kisspeptin is a key player in the central control of reproductive axis. Central administration of kisspeptin has been shown to advance puberty in rats. Stimulation of hypothalamic GnRH pulse generating mechanism by kisspeptin has been proposed to be the mechanism behind the onset of puberty. We hypothesized that chronic high doses of kisspeptin administration suppresses the reproductive axis and hence delays the pubertal onset. Hence, we investigated the effect of peripheral administration of chronic high doses of kisspeptin on pubertal onset, feed intake and body weight in female rats. Rats were treated with saline or kisspeptin (100 nmoles per day; intraperitoneal) for 26 days (day 25 to day 50 postnatal) and the day of vaginal opening was marked as day of puberty. Kisspeptin treated rats had delayed pubertal onset and reduced feed intake and body weight. Gonadal GPR54 mRNA was reduced suggesting that chronic high doses of kisspeptin may suppress the reproductive functions possibly by downregulation of GPR54 receptor. However, delay in puberty due to reduction in feed intake and body weight could not be ruled out in this study. Further, our study emphasizes the importance of dosage and duration of kisspeptin administration in the manipulation of reproductive axis. Our study, for the first time, suggests that kisspeptin and its analogues, if proven beneficial, could be used to treat precocious puberty in children. It appears that, though a promising tool for enhancing fertility, kisspeptin acts as a double-edged sword and has to be cautiously used to manipulate reproduction.

• Journal of Environmental Health Sciences
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• v.47 no.3
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• pp.245-258
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• 2021

Objectives: In many previous studies, endocrine disruptors (EDCs) have been found to affect delays in puberty. Various EDCs have been reported on, but there have been only limited epidemiologic studies on the effects of exposure to environmental heavy metals and pyrethroid pesticides on puberty delay. Therefore, the aim of this study was to investigate the association of exposure to environmental mercury, cadmium, and pyrethroid pesticides with delayed puberty in children based on national survey data that represents Korean children. Methods: We selected 450 children at the ages of 9-11 years old from the third Korean National Environmental Health Survey (3rd KoNEHS). The relations of urinary Hg, Cd, and 3-PBA with pubertal development were evaluated using multiple logistic regression analyses. Results: Urinary Hg levels were significantly associated with delayed puberty in boys [testicle development: OR=0.41 (95% CI: 0.20, 0.84); genitalia development: OR=0.35 (95% CI: 0.15, 0.81)]. Girls with higher Hg levels were more likely to experience delayed menarche [OR=0.23 (95% CI: 0.06, 0.90)]. We observed a significant 49% reduction in odds for menarche per increasing unit of urinary cadmium levels [OR=0.51 (95% CI: 0.24, 1.01)]. In addition, urinary 3-PBA showed a negative association with genitalia development in boys and menarche in girls [genitalia development: OR=0.73 (95% CI: 0.55, 0.96); menarche: OR=0.56 (95% CI: 0.32, 1.00)]. Conclusions: The results of this study support the hypothesis that exposure to environmental mercury, cadmium and pyrethroid pesticides may affect puberty delays. Additional evidence needs to be obtained through further prospective studies.

• The Journal of Korean Medicine
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• v.36 no.4
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• pp.150-155
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• 2015

The purpose of this report is to evaluate effect of Korean medical treatment on idiopathic gonadotropin-dependent precocious puberty (G-DPP) patient received herbal medicine. We administered Aesopjiyoun-tang remedy to idiopathic G-DPP and analyzed the delay effect by hormonal value and radiographs; the height growth effect by measurement of height. After Korean medical treatment, suppression effect to peak-Luteinizing Hormone level (LHL) is 14.39IU/L to 10.9IU/L for 13month, growth effect to height value is 11cm/13month; and change of mean growth velocity (MGV) is 6.08cm/year to 10.06cm/year. The gain in height by treatment is 3.98cm/year. The result suggests Aesopjiyoun-tang can be an effective treatment for G-DPP. Herbal medicine can be used as an alternative treatment in place of the GnRH treatment.

• Clinical and Experimental Pediatrics
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• v.52 no.3
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• pp.351-355
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• 2009

Purpose : This study compared bone ages measured by the Greulich-Pyle (GP) and Tanner-Whitehouse 3 (TW3) methods and investigated the differences in predicted adult heights measured by Bayley-Pinneau (BP) and TW3 methods. Methods : Bone ages were assessed from left-wrist radiographs by two investigators, one for each GP and TW3 methods in 85 normal children, 30 precocious puberty girls, and 30 constitutional growth delay boys. The differences between the measured predicted adult heights using the BP and TW3 methods were compared in each group. Results : The bone age measured by the TW3 method was less than that by the GP method in normal children. The predicted adult heights measured by the two methods showed no significant difference in normal boys, while the predicted adult height measured by the TW3 method was higher than that by the BP method for normal girls ($156.4{\pm}4.7$ cm vs. $158.9{\pm}3.8$ cm, P<0.01) and for precocious puberty girls ($156.3{\pm}4.0$ cm vs. $159.3{\pm}4.2$ cm, P<0.01). In contrast, the predicted adult height was higher from the BP method than from the TW3 method in constitutional growth delay boys ($173.3{\pm}4.4$ cm vs. $169.7{\pm}3.2$ cm, P<0.01). Conclusion : There were significant differences in predicted adult heights between the BP and TW3 method in normal girls, precocious puberty girls, or constitutional growth delay boys. In precocious puberty and constitutional growth delay, the BP method might be preferred to predict adult height, but further studies on final adult height are needed.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.1
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• pp.43-54
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• 1999

Klinefelter's syndrome is a very important disease in gynecologic endocrinologic fields, because the patients with this karyotype complain of infertility, azospermia and ambiguous genitalia. Y chromosome is an important chromosome which determine genetic sex and the structure of gonad and genitalia. In this study, to elucidate the cytogenetic characteristics and clinical features of Klinefelter's syndrome and Y chromosomal abnormalities in Korea, we studied 303 cases of Klinefelter's syndrome and 11 cases of Y chromosomal abnormalities which were diagnosed by chromosomal analysis at the Cytogenetic Laboratory, Institute of Reproductive Medicine and Population, Seoul National University for 12 years from January 1984 to December 1996. The results of this study showed as follows: 1. In a total of 9275 cases, there were 303 cases (3.3%) of Klinefelter's syndromes, 11 cases (0.1%) of Y chromosomal abnormalities. 2. In 102 cases of patients showed typical clinical features of Klinefelter's syndrome, 101 cases (99%) of them were diagnosed to Klinefelter's syndrome in karyotyping. 3. In 303 cases of Klinefelter's syndrome, there were 277 cases (91.4%) of 47,XXY complement, 16 cases (5.3%) of mosaicism, 2 cases (0.7%) of 48,XXXY, 5 cases (1.7%) of 48,XXYY and 3 cases (1.0%) of 49,XXXXY. 4. In 303 cases of Klinefelter's syndrome, 284 cases (93.7%) of them were diagnosed after puberty and only 19 cases (6.3%) of them were diagnosed before puberty. 5. In 303 cases of Klinefelter's syndrome, there were 146 cases (48.2%) of patients with infertility-associated chief complaints, 101 cases (33.3%) of patients with typical clinical features of Klinefelter's syndrome, 22 cases (7.3%) of patients with ambiguous genitalia. 6. In patients with Klinefelter's syndrome, 48,XXYY and 49,XXXXY had serious symptoms such as mental retardation, developmental delay, Down syndrome-like features, congenital anomalies, but 48,XXYY and other mosaicisms had infertility-associated symptoms or ambiguous genitalia. 7. The 8 cases of polysomy Y (XYY complement) showed several serious symptoms such as Down syndrome-like features, mental retardation, fragile X syndrome-like feature, congenital anomalies, ambiguous genitalia which could be detected before puberty.

• Environmental Analysis Health and Toxicology
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• v.21 no.3 s.54
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• pp.291-299
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• 2006

The experiments investigated whether early exposure to testosterone propionate (TP) during prepuberty alters testis development in Sprague-Dawley male rats. We performed Hershberger assay using the stimulated weanling male rats by OECD protocols, cDNA microarray, and Western blot. TP was subcutaneously injected to uncastrated Sprague-Dawley male rat of 22 days old for 10 consecutive days at doses of 0.4, 0.8, 1.0, 1.2, 1.6 mg/kg per day. At necropsy, the following tissues were removed and weighed: combined testes, epididymides (Epi), Cowper's glands (COW), levator am, and bulbocavernosus muscles (LABC), seminal vesicles, together with coagulating gland (SV) and ventral prostate (VP). We found that TP increased the weights of Epi, VP, SV, COW, and LABC, while testis was decreased in a dose-dependent manner. In cDNA microarray analysis of testis, there were significant reductions in the expression of cytochrome P450 11A (CYP11A), the rate-limiting enzyme of steroidogenesis. Taken together these results, TP exposure before puberty in male rats may produce the delay in testis development by inhibiting the CYP11A gene expression.

• 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.

• Journal of Embryo Transfer
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• v.18 no.3
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• pp.249-255
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• 2003

These studies were performed to improve the reproductive efficiency of gilts and we investigated the effects of puberty periods, first mating time and backfat thickness and will adapt to these results for early selection of excellent gilts. The main results were as follows; 1. First heats on birth season were showed 194.14 day, 163.25 day, 160.25 day and 157.92 day at birth of spring, summer, autumn and winter, respectively and birth of spring was significantly latest among other seasons (p<0.01). 2. First service on birth season were revealed 222.05 day in spring, 193.00 day in summer, 199.20 day in autumn and 190.11 day in winter. birth of spring was significantly latest among others (p<0.01). 3. First heat period of cadidated gilt had 13∼16 mm backfat thickness was 180.32 day, 171.24 day in 17∼20 mm and 162.20 day in 21∼23 mm and was showed delay in thin backfat gilts. There was no differences among backfat thickness. 4. First service of cadidate gilt had 13∼16mm backfat thickness was 211.12 day, 202.43 day in 17∼20 mm and 195.43 day in 21∼23 mm and was showed delay in thin backfat gilts. There was no differences among backfat thickness. 5. The litter size were 9.64 in gilts under 160 day of first heat, 10.14 in 161∼180 day, 9.56 in 181∼200 day and 9.13 in over 201 day. There showed the largest litter size in 161∼180 day of first heat but was no differences. 6. The litter size in gilts under 180 day of first service was 9.13, 9.75 in 181∼200 day, 10.13 in 201∼220 day and 9.45 in over 221 day. There showed the largest litter size in 201∼220 day of first service but was no differences. 7. The litter size of gilt had 13∼16 mm backfat thickness on first service was 9.33, 9.81 in 17∼20 mm and 10.17 in 21∼23 mm and was showed delay in thin backfat gilts. There was no differences among backfat thickness.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2002.10a
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• pp.168-168
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• 2002

To establish a test protocol for the rodent 20-day thyroid/pubertal assay, flutamide and diethylstilbestrol (DES) were administered to intact male Sprague-Dawley rats from postnatal day 33 for 20 days. Flutamide (1, 5, and 25 mg/kg/day) or DES (10, 20, and 40 ug/kg/day) was given once daily by oral gavage to immature male rats. Prepuce separation was significantly delayed in flutamide group and in DES group. One day after the last dose, the rats were killed and pituitary, thyroid, and reproductive organs were removed and weighed. Flutamide treatment resulted in a significant reduction in the weights of epididymides, ventral prostate, seminal vesicles plus coagulating glands and fluid (SVCGF), levator ani. bulbocarvenus muscles (LABC), Cowper's glands, and glans penis. The weight of adrenal glands decreased at % mg/kg/day, while testes and any other organ weights were unaffected. No microscopic changes were observed in the thyroid glands. Serum levels of testosterone wert significantly increased in the flutamide-treated groups and serum levels of estradiol were also increased. A significant reduction in the weights of testes, epididymides, ventral prostate, SVCGF, LABC, Cowpers glands, and glans penis of DES treated group. Serum testosterone and LH decreased significantly in DES group. Decrease of estradiol was observed, but not significant. These results indicate that flutamide and DES delay puberty in the male rat and its mode of action appears to be via altered secretion of steroids, which subsequently affect the development of the reproductive tract. (Supported by the grant from NITR/Korea FDA for Endocrine Disrupter Research.)