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.

Sperm recovery from epididymis in animals considered as important tools to preserve high-value or endangered species. However, there are no appropriate castrating indicators of timing for recovery of sperm which can be available to artificial reproduction technologies such as artificial insemination (AI) and in vitro fertilization (IVF), particularly in young Hanwoo bull. Therefore, this study aimed to investigate semen volume, morphology and motility of sperm in epididymis of young Hanwoo bulls at 8, 13, 14, and 15 months of age. About 2 cm of the epididymal tail only was cut and minced using blades. Minced epididymal tail tissues were mixed with semen extender (OptixCell, France, IMV technologies) and sperm were recovered with a cell strainer (100 μm nylon mesh). The number of sperm at 8 months of age was lower than that at 13, 14, 15 months of age in bulls after collection (33.6±27.2 vs. 352.4±39.2, 320.4±113.6 and 422.8±252.4×107cells respectively; P<0.05). After the frozen-thawed sperm the the percentage of abnormal head, tail and dead damaged acrosome did not differ between the ages 13, 14 and 15 months of age in bulls (P>0.05), however, the dead sperm with intact acrosome (DIA), the numbers showed that more than 15 months in 8, 13, 14 months (8.7±4.1 vs. 47.3±12.2, 34.8±14.0, 28.8±8.5, P<0.05). In addition, frozen-thawed sperm at 8 months of age showed low total motile sperm compared to those at 13, 14 and 15 months of age (26.4±8.2 vs. 45.7±29.5, 62.3±41.0, 70.4±15.9%, respectively; P<0.05). In conclusion, sperm derived from epididymal tail at 8 months of age in Hanwoo bulls showed high abnormal morphology and poor motility, which is not adequate for artificial insemination(AI) and in vitro fertilization(IVF). On the other hand, sperm derived from epididymal tail at 13, 14, 15 months of age in bull showed high normal morphology and motility, which may be available for AI and IVF. Epididymal sperm collected from bulls over 13 months is needed for further study whether to use the actual in vitro fertilization.

The purpose of this study was to investigate improvement of food habits and eating behavior in children with obesity andprecocious puberty by nutritional education monitoring. The results are as follows. Average height and weight of subjectsexceeded Korean height and weight standards for children as outlined by The Korea Pediatric Society. Using nutritioneducation monitoring, meals became more regular, overeating significantly decreased, and eating speed decreased. Further,frequencies of eating-out and night-eating significantly decreased. The most preferred menu item when eating-out wasKorean food, and the most preferred menu item for night-eating was fruits, fast food, & processed food. Meat & fish andvegetable intakes all significantly increased. Fruit and milk intakes also significantly increased while bread, snack, and icecream intakes decreased. Further, fast food & instant food intakes decreased. However, water intake was not significantlyaffected. The favorite food of children was meat & fish, followed by fast food & processed food. This study may provideinformation on dietary behavior of children with obesity and precocious puberty and suggests that nutrition education orcounseling can improve food habits and eating behavior.

Although the majority of surviving pigs cloned by somatic cell nuclear transfer (SCNT) appear to be physiologically normal, there is a general lack of detailed hemato-physiologic studies for the period of early adulthood to substantiate this claim. In the present study, we investigated variation in blood chemistry and endocrinological parameters between mesenchymal stem cells (MSCs) derived from cloned and normal age-matched female and male miniature pigs. Cloned females and males showed normal ranges for complete blood count assessments. Biochemical assessments showed that γ-GGT, ALT and cholesterol levels of male and female clones were significantly (P<0.05 or P<0.01, respectively) higher than that of age-matched control miniature pigs. Variations in insulin and IGF-1 were higher in female clones than in male clones and controls. Thus, although female and male cloned miniature pigs may be physiologically similar to normal animals, or at least within normal ranges, a greater degree of physiological and endocrinological variation was found in cloned pigs. The above variation must be taken into account before considering cloned female or male miniature pigs for various biomedical applications.

Background & Objectives: Methoxychlor(MET), an organochlorine insecticide, has been thought a potent endocrine disrupting chemical. The present study was undertaken to examine whether short-term exposure to MET can alter the onset of puberty and the associated reproductive parameters such as hormone receptor expressions in prepubertal female rats. Method: MET (1, 10 and 100 mg/kg/day) was administered daily from postnatal day 25 (PND 25) through the PND 34, and the animals were sacrificed on the PND 35. The first V.O. day was monitored, and the weights of reproductive tissues were measured. To assess the structural alterations in the ovary and uterus, the tissues were embedded in paraffin and stained for histological analysis. The transcriptional activities of hypothalamic and pituitary genes were measured using quantitative RT-PCRs. The uterine and hypothalamic proteins were extracted and used for the ER western blotting. Results: As a result, 100 mg group showed advanced V.O. than control, 1 mg group and 10 mg group. The wet weights of ovaries from MET-treated animal dose-dependently increased. The uterine weights were increased in 1 mg group and 10 mg group, while the 100 mg group samples were not significantly different from control tissues. The adrenal, kidney, spleen and thymus weights were not shown any significant change. Corpora lutea and fully grown follicles were observed in the ovaries from the 100 mg group, while numerous primary and secondary follicles were observed in the ovaries from control group. Myometrial thickness of MET-treated group was dose-dependently increased. Epithelial hypertrophy and well-developed glands were observed in the uterus from the 10 mg groups. Conclusions: The present study demonstrated that the short-term exposure to MET during the critical period of prepubertal stage could activate a reproductive endocrine system, resulting the early onset of puberty in immature female rats. Our study suggests that MET’s disrupting effect might be derived from premature activation of key reproduction-related genes in hypothalamus-pituitary neuroendocrine circuit.

The aim of this study was to investigate the clinical relations of eating behaviors to body mass index (BMI) and obesity in girls with idiopathic central precocious puberty. This study included 30 precocious puberty patients who were diagnosed at Chosun University Hospital between February and December 2013. Information was obtained from their parents using a questionnaire focused on eating behaviors and lifestyle factors. We rechecked their BMI and questionnaire after 12 months to identify the changes. Six (20%) of the 30 patients children were overweight and obesity at diagnosis. Overweight and obesity group tended to overeat. Normal weight group ate an unbalanced diet more than overweight and obesity group, particularly lack of fruit and vegetable (p=0.010). Eight (27%) of the 30 patients children were overweight and obesity and 24 (80%) of the 30 patients children showed increased BMI after 12 months follow up. BMI-decreased group ate breakfast with whole family members more frequent than BMI-increased group (p=0.006). This study showed the importance of healthy diet during treatment of precocious puberty. Children with precocious puberty should avoid overeating and make a balanced diet with preferable eating behaviors from the family meals.

스테로이드 호르몬은 다양한 생리작용의 조절자로서 잘 알려져 있으며, 생리적 활성에 따라 5그룹 (mineralocorticoids, glucocorticoids, estrogens, progestagens, androgens)으로 나뉜다. 그 중 estrogen류는 특히 암컷 포유류의 이차성징을 유도함이 잘 알려져 있다. 본 연구는 사춘기 전후 암컷 흰쥐난소에서의 steroidogenesis 조절 효소의 유전자 발현에 대해 정밀 조사한 것이다. 미성숙한 암컷 흰쥐를 생후 29일에서 43일까지 2일 간격으로 희생한 뒤 total RNA를 추출하여 semi-quantitative RT-PCR을 시행하여 steroidogenesis 관련유전자인 StAR(steroidogenic acute regulatory protein), CYP11A1(side-chain cleavage enzyme), CYP17(17α-hydroxylase), 3β-HSD(3β-hydroxysteroid dehydrogenase), 17β-HSD(17β-hydroxysteroid dehydrogenase), CYP19(Aromatase)의 발현 양상을 조사하였다. 연구에 사용된 암컷 흰쥐는 대체로 37일에 질구개방이 일어났다. 유전자 발현 조사에서 StAR는 생후 41일, 43일에 유의하게 증가(p<0.05, p<0.01)하였다. CYP11A1은 43일에 유의하게 증가(p<0.01)하였다. CYP17의 경우, 35일과 39일에서 유의한 감소(각 p<0.05)를 보였다. 3β-HSD, 17β-HSD, CYP19의 경우는 유의한 변화를 보이지 않았다. 전반적으로 스테로이드 합성 관련 유전자 모두 생후 35일에 감소하였다가 암컷의 성 성숙 지표인 질구개방이 대체로 일어난 37일을 기준으로 유전자 발현이 급증됨을 확인하였다. 이는 사춘기 개시를 위한 다량의 sex steroid 합성을 위한 것으로 추정된다. 이러한 결과는 사춘기 전후시기 난소의 성 성숙에 관한 기초자료로 사용될 수 있을 것으로 사료된다.

시상하부-뇌하수체-부신(HPA) 축은 생리적, 심리적 스트레스와 관련된 호르몬의 분비를 조절하는 신경 내분비 축이다. 이전의 보고에 따르면 신체적 및 정신적 스트레스에 의한 HPA 축반응이 사춘기 발달과 관련이 있다고 알려져 있다. 본 연구는 암컷 흰쥐의 사춘기 전후 시기에시상하부-뇌하수체-부신 축에서 스테로이드 호르몬합성 유전자들의 활성 변화를 날짜별로 조사한 것이다. 생후 29일의 암컷 흰쥐를 사춘기 개시 이후 시기인 43일까지 2일 간격으로 희생하였다. HPA 축에서 스테로이드합성 관련 유전자들의 발현 변화를 조사하기 위해 semi-quantitative RT-PCR을 실행하였으며, 방사면역측정법(RIA)를 통해 혈청 내 코르티코스테론(corticosterone) 수준을 측정하였다. 시상하부에서 CRH를 발현을 조사한 결과 생후 35일까지는 다소 증가하다가 37일부터 감소하는 경향을 보인 후 생후 43일(p<0.05)에 다시 유의하게 증가하였다. GR 발현은 유의한 양상은 나타나지 않았다. 뇌하수체에서 ACTH mRNA 수준은 생후 33일까지 다소 증가하다가 35일부터 43일까지 점차적으로 감소하는 경향은 보이지만, 유의성은 없었다. 부신에서 StAR mRNA 수준은 점차적으로 감소하다가 생후 35일(p<0.05), 37일(p<0.05)에서 유의하게 감소하였고, 생후 39일에 다소 증가하였다가 다시 감소하여 43일(p<0.01)에서 유의하게 감소하였다. CYP11A1의 발현 역시 StAR와 유사한 양상을 보이며, 생후 35일(p<0.05), 37일(p<0.05)에서 유의하게 감소하는 양상을 보였다. 또한 3β-HSD의 발현은 전체적으로 감소하여 생후 35일(p<0.05)에서 39일(p<0.01)까지 유의하게 감소하였고, 생후 41일에 다소 증가한 후 43일(p<0.01)에서 유의하게 감소하였다. CYP11B1과 CYP21A의 발현을 조사한 결과, CYP11B1은 생후 31일(p<0.01)부터 35일(p<0.01)까지 크게 감소하고, 37일에서 증가한 후 다시 감소하여 생후 39일(p<0.05), 43일(p<0.05)에서 유의하게 감소하였다. CYP21A 발현은 생후 37일(p<0.01)까지 크게 감소하고 39일 부터 증가하는 양상을 보였다. 혈중 코르티코스테론의 경우 생후 31일(p<0.01)부터 35일(p<0.01)까지 유의하게 증가하고 37일부터 감소하는 경향을 보였다. 본 연구를 통해 사춘기 개시 전후 시기에 HPA 축에서 스테로이드합성 관련 유전자들의 발현 패턴이 동적으로 변화하며, 부신에서 효소들이 생후 35일경에 대체로 감소하는 양상을 확인하였다. 이는 사춘기 개시에 관여하는 HPG 축과 부신 축인 HPA 축간의 상호 조절 시스템이 존재하며 사춘기 개시 시점에 부신에서의 스테로이드합성이 어떠한 영향을 받을 수 있다는 가능성을 시사한다.

현재, 사춘기 전후 시기의 수컷 흰쥐의 성 성숙에 대한 연구가 활발히 이루어지고 있으나, 전반적인 사춘기 시기에 이루어지는 수컷 흰쥐 생식기관의 발달에 대한 연구는 부족한 실정이다. 이에 본 연구에서는 수컷 흰쥐의 성 성숙 발달 지표인 Anogenital distance(AGD)에 근거하여 사춘기 개시시기인 생후 25일부터 완전한 성 성숙이 이루어진 생후 50일 경까지 수컷 흰쥐에서 이루어지는 생식기관의 조직학적 발달을 조사하였으며, 이를 완전한 성체인 생후 70일의 수컷 흰쥐의 생식기관과 비교하였다. 생후 25일의 수컷 흰쥐를 5일 간격으로 생후 50일까지 조사하였으며, 성체인 생후 70일의 수컷 흰쥐도 함께 조사하였다. 오전 10시에 체중을 측정한 후 일괄 희생하여 생식기관 무게 및 AGD를 측정하였다. 정소를 포함한 부속생식기관들은 Hematoxylin & Eosin 염색법을 사용하여 조직학적 조사를 시행하였다. 체중은 생후 25일부터 생후 70일까지 유의하게 증가(P<0.01)하였으며, 정소와 부정소의 무게 또한 생후 25일부터 생후 70일까지 유의하게 증가(P<0.01)하였다. 저정낭은 생후 25일부터 생후 45일까지 점차적으로 증가(P<0.05)하다가 생후 50일부터 급격하게 증가하였다(P<0.01). 전립선의 경우 생후 25일부터 생후 35일까지 점진적으로 증가(P<0.05)하다가 생후 40일부터 급격하게 증가(P<0.01)하였다. AGD는 생후 25일부터 생후 70일까지 유의하게 증가(P<0.01)하였다. 조직학적 조사 결과, 정소는 생후 25일부터 점진적인 성숙으로 인해 세정관의 크기가 커짐이 관찰되었고, 생후 45일까지는 세정관 내 정자를 관찰할 수 없었으나, 생후 50일부터 세정관 내 정자를 확인할 수 있었다. 부정소 역시 점차적인 성숙으로 인해 생후 25일부터 도관의 내강이 커져 면적이 크게 증가하는 것을 확인하였으며, 생후 50일부터 도관 내 정자를 관찰할 수 있었다. 전립선과 저정낭의 경우 생후 25일부터 생후 70일까지 내강의 면적이 증가하여 점진적인 성숙이 이루어지는 것을 확인하였다. 본 연구에서는 AGD 측정을 통해 생후 25일부터 꾸준한 정소하강이 발생하여 생후 50일부터는 완전한 성 성숙이 이루어짐을 확인하였다. 또한 조직학적 연구를 통해 생식기관에서 이루어지는 성 성숙과 실제로 정자가 형성되는 시기를 확인하였다. 이후 지속적인 연구를 통해 수컷 포유류의 사춘기 개시에 이르기까지의 생식기관의 성숙 과정을 보다 정밀하게 조사할 필요가 있으며, 이를 통해 수컷 포유류의 사춘기 개시에 관여하는 다양한 조절 인자의 기능을 규명할 수 있을 것으로 기대한다.

In mammals, puberty is a dynamic transition process from infertile immature state to fertile adult state. The neuroendocrine aspect of puberty is started with functional activation of hypothalamus-pituitary-gonadal hormone axis. The timing of puberty can be altered by many factors including hormones and/or hormone-like materials, social cues and metabolic signals. For a long time, attainment of a particular body weight or percentage of body fat has been thought as crucial determinant of puberty onset. However, the precise effect of high-fat (HF) diet on the regulation of hypothalamic GnRH neuron during prepubertal period has not been fully elucidated yet. The present study was undertaken to test the effect of a HF diet on the puberty onset and hypothalamic gene expressions in immature female rats. The HF diet (45% energy from fat, HF group) was applied to female rats from weaning to around puberty onset (postnatal days, PND 22-40). Body weight and vaginal opening (VO) were checked daily during the entire feeding period. In the second experiment, all animals were sacrificed on PND 36 to measure the weights of reproductive tissues. Histological studies were performed to assess the effect of HF diet feeding on the structural alterations in the reproductive tissues. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus, total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Body weights of HF group animals tend to be higher than those of control animals between PND 22 and PND 31, and significant differences were observed PND 32, PND 34, PND 35 and PND 36 (p<0.05). Advanced VO was shown in the HF group (PND p<0.001) compared to the control (PND ). The weight of ovaries (p<0.01) and uteri (p<0.05) from HF group animals significantly increased when compared to those from control animals. Corpora lutea were observed in the ovaries from the HF group animals but not in control ovaries. Similarly, hypertrophy of luminal and glandular uterine epithelia was found only in the HF group animals. In the semi-quantitative RT-PCR studies, the transcriptional activities of KiSS-1 in HF group animals were significantly higher than those from the control animals (p<0.001). Likewise, the mRNA levels of GnRH (p<0.05) were significantly elevated in HF group animals. The present study indicated that the feeding HF diet during the post-weaning period activates the upstream modulators of gonadotropin such as GnRH and KiSS-1 in hypothalamus, resulting early onset of puberty in immature female rats.

Dicarboximide계 살균제인 vinclozolin(VCZ)은 과일, 야채, 관상용 식물에서 미생물에 의해 유발되는 병들을 통제하는데 사용되어왔다. VCZ의 대사산물인 M1과 M2는 흔히 토양, 식물, 포유류에 잔존하기 때문에 인간에게 노출될 가능성이 크다. VCZ가 갖는 항안드로겐성 활성 때문에 주로 수컷에 대한 연구가 이루어졌으며, 암컷의 사춘기와 생식계에 미치는 영향은 연구가 미비한 실정이다. 따라서 본 연구는 VCZ가 암컷 흰쥐의 사춘기 개

전세계적으로 매년 대량생산되는 프탈레이트(phthalate)류 물질은 플라스틱처럼 다양한 생활용품의 원료로 사용되기 때문에 인간에 대한 노출 정도가 매우 높은 산업 물질이다. 대표적으로 di(2-ethyl hexyl)phthalate(DEHP)와 그 활성 대사물인 monoethyl hexyl phthalate(MEHP)가 내분비계 장애물질(endocrine disruptor)로 작용하여 인간과 실험 동물의 생식계를 교란한다는 증거들이 급속히 축적되고 있

콩류 섭취가 유방암이나 골다공증, 그리고 심혈관계 질환 예방에 도움이 된다는 사실은 학계는 물론 일반인들에까지 큰 관심을 불러 일으키고 있다. 그러나 콩류, 특히 그 주성분인 genistein(GS)이 상기한 긍정적인 효과 외에도 여성의 생식계에 잠재적으로 부정적인 영향을 미칠 가능성에 대한 의문이 계속되어 왔다. 본 연구에서는 GS가 암컷 흰쥐의 사춘기 개시에 미치는 효과와 호르몬 수용체 등 이때의 다양한 생식 지표들의 변화들 조사하였다. GS(100