• Animal cells and systems
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• 제4권4호
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• pp.367-373
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• 2000

In the present study we determined if NELL2, a neural tissue-specific protein containing 6 epidermal growth factor (EGF)-like repeat domains, plays an important role in the regulation of puberty initiation in the rat hypothalamus. We origin811y found that NELL2 is a new estrogen-responsive gene in hypothalami derived from estrogen-sterilized and control rats using a PCR differential display. In the 40-day-old female rat hypothalamus, NELL2 was up-regulated by neonatal estrogen treatment. In situ hybridization histochemistry showed that NELL2 is very abundant in the ventromedial hypothalamic nucleus that is responsible for the control of sex behavior. NELL2 mRNA level in the medial basal hypothalamus showed a dramatic increase before female puberty onset, which suggests that NELL2 may be involved in the process regulating female puberty onset. We attemped to block NELL2 synthesis with intracerebroventricular injection of an antisense oligodeoxynucleotide (ODN) to the NELL2 mRNA, and examined its effect on the puberty onset of the female rat. The antisense ODN significantly delayed puberty initiation determined by vaginal opening. In summary, NELL2 may play an important role in the regulation of female puberty onset.

• 한국발생생물학회지:발생과생식
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• 제20권2호
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• pp.91-99
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• 2016

Lipopolysaccharide (LPS), an endotoxin, elicits strong immune responses in mammals. Several lines of evidence demonstrate that LPS challenge profoundly affects female reproductive function. For example, LPS exposure affects steroidogenesis and folliculogenesis, resulting in delayed puberty onset. The present study was conducted to clarify the mechanism underlying the adverse effect of LPS on the delayed puberty in female rats. LPS was daily injected for 5 days ($50{\mu}g/kg$, PND 25-29) to treated animals and the date at VO was evaluated through daily visual examination. At PND 39, animals were sacrificed, and the tissues were immediately removed and weighed. Among the reproductive organs, the weights of the ovaries and oviduct from LPS-treated animals were significantly lower than those of control animals. There were no changes in the weights of uterus and vagina between the LPS-treated and their control animals. immunological challenge by LPS delayed VO. Multiple corpora lutea were found in the control ovaries, indicating ovulations were occurred. However, none of corpus luteum was present in the LPS-treated ovary. The transcription level of steroidogenic acute regulatory protein (StAR), CYP11A1, CYP17A1 and CYP19 were significantly increased by LPS treatment. On the other hand, the levels of $3{\beta}$-HSD, $17{\beta}$-HSD and LH receptor were not changed by LPS challenge. In conclusion, the present study demonstrated that the repeated LPS exposure during the prepubertal period could induce multiple alterations in the steroidogenic machinery in ovary, and in turn, delayed puberty onset. The prepubertal LPS challenge model used in our study is useful to understand the reciprocal regulation of immune (stress) - reproductive function in early life.

• Animal cells and systems
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• 제3권3호
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• pp.319-329
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• 1999

Onset of female puberty follows a series of prepubertal cellular and molecular events including changes of synaptic plasticity, synthetic and releasing activity and gene expression. Dramatic increase of gonadal steroid level is one of the most prominent changes before the onset of puberty. Based on the importance of steroid feedback upon the hypothalamus, we adopted an estrogen sterilized rat (ESR) model where 100 ng of 17$\eta$-estradiol were administered into neonatal pubs for 7 days after birth. To identify genes involved in the onset of female puberty, we applied PCR differential display using RNA samples derived from ESR and control rat hypothalami. About 100 out of more than 1000 RNA species examined displayed differential expression patterns between a 60-day old control rat and ESR. Sequence analysis of differentially amplified PCR products showed homology with genes such as mouse kinesin superfamily-associated protein 3 (KAP3) and several cDNAs previously described by others in mouse and human tissues. Several gene products such as 2-1 and 8-1 corresponded to novel DNA sequences. We analyzed mRNA levels of KAP3, 2-1 and 8-1 genes in the hypothalami derived from neonatal, 6-, 28-, 31-, and 40-day old rats. Northern blot analysis showed that mRNAs of KAP3, 2-1 and 8-1 genes were markedly increased before the initiation of puberty. Neonatal treatment of estrogen clearly inhibited prepubertal increases in KAP3, 2-1 and 8-1 mRNA levels. Therefore, these genes may play important roles in the initiation of hypothalamic puberty. In addition, intracerebroventricular (icv) injection of antisense KAP3 oligodeoxynucleotide (ODN) clearly delayed puberty initiation determined by vaginal opening, which further confirmed that KAP3 plays an important role in the regulation of puberty initiation.

• Molecules and Cells
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• 제22권1호
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• pp.30-35
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• 2006

Munc18, a mammalian homolog of C. elegans Unc, is essential for neurotransmitter release. The aim of this study was to identify estrogen-dependent expression of Munc18-1 and its role in the regulation of glutamate release for puberty onset. Hypothalamic munc18-1 mRNA levels were significantly increased by estrogen treatment in ovariectomized, immature female rats. During pubertal development, the munc18-1 mRNA levels dramatically increased between the juvenile period and the anestrous phase of puberty. Intracerebroventricular administration of an antisense oligodeoxynucleotide against munc18-1 mRNA significantly decreased glutamate release and delayed the day of puberty onset. These results suggest that Munc18-1, expressed in an estrogen-dependent manner, plays an important role in the onset of female puberty via the regulation of glutamate release.

• 한국동물생명공학회지
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• 제36권1호
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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.

• 한국발생생물학회지:발생과생식
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• 제4권1호
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• pp.109-114
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• 2000

본 연구는 사춘기전과 사춘기가 시작될 무렵의 흰쥐난소에서 에탄올이 steroidogenic acute regulatory protein(StAR)의 유전자 발현에 어떠한 영향을 미치는지 조사하고자 수행되었다. 생후 25일 째부터 매일 흰쥐에 에탄을 또는 생리식염수를 복강주사하고 생후 27일, 32일 째에 실험동물을 희생시켜 혈액과 난소를 적출하였다. 실험결과 에탄올은 혈중의 황체호르몬 함량을 유의하게 감소시켰으며, 자궁의 무게는 27일 째에는 에탄올처리군에서 유의하게 적었으나, 32일 째에는 차이를 나타내지 않았다. 사춘기의 시작을 나타내는 지표의 하나인 viginal opening은 에탄올처리군에서 현저히 지연되었으며, 난소에서의 StAr mRNA발현 또한 유의하게 감소됨을 알 수 있었다. 따라서 본 연구결과는 에탄올이 적어도 사춘기 난소의 기능 및 사춘기의 시작을 교란시킬 수 있으며, 이러한 영향의 일부는 난소내 StAR유전자 발현을 억제함으로써 나타난다고 사료된다.

• 대한지역사회영양학회지
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• 제5권1호
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• pp.50-62
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• 2000

This study was conducted with 20 female gymnasts to examine the relationship between eating patterns, diet menstrual function and hematological status. According to the baseline data a nutrition counseling and education program was developed and evaluated improved the nutritional status and health of female gymnasts. Mean body weight at the onset of the study was 42.1$\pm$7.0kg and was reduced to 41.8$\pm$6.1kg after the nutrition counseling and education program. The percent of body fat was significantly reduced from 13.9$\pm$3.7% to 13.1$\pm$3.1%(p<0.01) skinfold thickness of subscapular and thighs was reduced significantly(p<0.01, p<0.05) Mean daily intake levels of energy, protein calcium iron thiamin riboflavin and niacin were significantly elevated after the nutrition counseling and education program but were lower than the Recommenced Dietary Allowances. For the nutrition knowledge and food habits, the posttest mean scores showed a significant increase. The hematological status(hematocrit, serum ferritin) and the early follicle level of estradiol were elevated to a mild degree although it was not significant,. The follicular stimulating hormone level was elevated significantly(p<0.01) Gymnastica has been one of the sports implicated by the medical profession as having probable detrimental effects. The implications of such training to childs growth and maturation have yet to be determined . Most female athletes, however, experience poor nutritional status and delayed puberty The priorities were to prepared a more effective nutrition program and education material status and delayed puberty. The priorities were prepared a more effective nutrition program and educational material for athletes coaches and adminstrators to prepare guidelines for the team physicians and coaches to follow for the physical and physiological examinations of female athletes.

• Clinical and Experimental Pediatrics
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• 제49권12호
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• pp.1257-1262
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• 2006

The age of puberty represents a very critical time in the life history of every young woman. The menarche stands as primary indicator of the onset of sexual maturation in females. By late adolescence, 75% of girls experience some problem associated with menstruation. Delayed, irregular, painful, and heavy menstrual bleeding are leading reasons for physician office visits by adolescents, and dysmenorrhea is the leading reason for school absenteeism among girls. This article discusses normal menstrual function during adolescence, then reviews the clinical presentation, evaluation, and management of adolescent dysmenorrhea, dysfunctional uterine bleeding, amenorrhea, and polycystic ovary syndrome.

• Clinical and Experimental Pediatrics
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• 제57권11호
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• pp.465-471
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• 2014

Inflammatory bowel disease (IBD) is a chronic relapsing disorder of unknown etiology, which is believed to be multifactorial. Recently, the incidence of pediatric IBD has steeply increased in Korea since 2000. Poorly controlled disease activity can result in complications such as intestinal fistulae, abscess, and stricture, as well as growth retardation and delayed puberty in children. Because of a lack of confirmative tests, various diagnostic modalities must be used to diagnose IBD. Onset age, location, behavior, and activity are important in selecting treatments. Monogenic IBD must be excluded among infantile and refractory very-early-onset IBD. Early aggressive therapy using biologics has recently been proposed for peripubertal children to prevent growth failure and malnutrition.

• Molecules and Cells
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• 제41권12호
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• pp.1024-1032
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• 2018

The central mechanisms coordinating growth and sexual maturation are well conserved across invertebrates and vertebrates. Although mutations in the gene encoding makorin RING finger protein 3 (mkrn3) are associated with central precocious puberty in humans, a causal relationship has not been elucidated. Here, we examined the role of mkrn1, a Drosophila ortholog of mammalian makorin genes, in the regulation of developmental timing. Loss of MKRN1 in $mkrn1^{exS}$ prolonged the $3^{rd}$ instar stage and delayed the onset of pupariation, resulting in bigger size pupae. MKRN1 was expressed in the prothoracic gland, where the steroid hormone ecdysone is produced. Furthermore, $mkrn1^{exS}$ larvae exhibited reduced mRNA levels of phantom, which encodes ecdysone-synthesizing enzyme and E74, which is a down-stream target of ecdysone. Collectively, these results indicate that MKRN1 fine-tunes developmental timing and sexual maturation by affecting ecdysone synthesis in Drosophila. Moreover, our study supports the notion that malfunction of makorin gene family member, mkrn3 dysregulates the timing of puberty in mammals.