• Animal cells and systems
• /
• v.4 no.4
• /
• pp.367-373
• /
• 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.

• Animal cells and systems
• /
• v.3 no.3
• /
• pp.319-329
• /
• 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.

• Journal of Digital Convergence
• /
• v.12 no.9
• /
• pp.283-290
• /
• 2014

Recently, As the prevalence of precocious is increased in Korea This study was evaluated the physical growth and female sex hormone characteristics of girls with Idiopathic precocious puberty. Retrospective analysis about the medical record of 113 girls for evaluation of signs of precocious puberty except for organic causes was done. Physical growth features and Female sexual hormone were analyzed. Height SDS and Weight SDS were significantly increased in true sexual precocity compared to pseudo sexual precocity. Hormone studies showed that the level of basal LH, FSH, E2 was significantly higher in true precocious puberty. The finding of this study suggest that we need to develop intervention about physical and psychological problems for precocious puberty girls.

• Development and Reproduction
• /
• v.13 no.3
• /
• pp.183-190
• /
• 2009

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 $32.8{\pm}0.37$ p<0.001) compared to the control (PND $38.25{\pm}0.25$). 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.

• Molecules and Cells
• /
• v.22 no.1
• /
• pp.30-35
• /
• 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.

• Development and Reproduction
• /
• v.14 no.1
• /
• pp.35-41
• /
• 2010

Mammalian reproduction is regulated by a feedback circuit of the key reproductive hormones such as GnRH, gonadotropin and sex steroids on the hypothalamic-pituitary-gonadal axis. In particular, the onset of female puberty is triggered by gain of a pulsatile pattern and increment of GnRH secretion from hypothalamus. Previous studies including our own clearly demonstrated that genistein (GS), a phytoestrogenic isoflavone, altered the timing of puberty onset in female rats. However, the brain-specific actions of GS in female rats has not been explored yet. The present study was performed to examine the changes in the activities of GnRH neurons and their neural circuits by GS in female rats. Concerning the drug delivery route, intracerebroventricular (ICV) injection technique was employed to eliminate the unwanted actions on the extrabrain tissues which can be occurred if the testing drug is systemically administered. Adult female rats (PND 100, 210-230 g BW) were anaesthetized, treated with single dose of GS ($3.4{\mu}g$/animal), and sacrificed at 3 hrs post-injection. 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). ICV infusion of GS significantly raised the transcriptional activities of enhanced at puberty1 (EAP-1, p<0.05), glutamic acid decarboxylase (GAD67, p<0.01) which are known to modulate GnRH secretion in the hypothalamus. However, GS infusion could not change the mRNA level of nitric oxide synthase 2 (NOS-2). GS administration significantly increased the mRNA levels of KiSS-1 (p<0.001), GPR54 (p<0.001), and GnRH (p<0.01) in the hypothalami, but decreased the mRNA levels of LH-$\beta$ (p<0.01) and FSH-$\beta$ (p<0.05) in the pituitaries. Taken together, the present study indicated that the acute exposure to GS could directly activate the hypothalamic GnRH modulating system, suggesting the GS's disrupting effects such as the early onset of puberty in immature female rats might be derived from premature activation of key reproduction related genes in hypothalamus-pituitary neuroendocrine circuit.

• 대한생식의학회:학술대회논문집
• /
• 2006.06a
• /
• pp.171.2-171.2
• /
• 2006

• Development and Reproduction
• /
• v.17 no.1
• /
• pp.55-62
• /
• 2013

Puberty is the developmental period which animals obtain the ability of reproducing sexually for the first time in life. In commercially important aquaculture fish species, the onset of puberty is a matter of major interest due to controlling of sexual maturation to improve broodstock management. To investigate pubertal characteristics of female longtooth grouper (Epinephelus bruneus), specimens were classified into three groups by the bodyweight, including 1, 2, and 3 kg group. Thereafter, we focused on ovarian development and level changes of endocrine regulation factors (GnRH, GTHs, steroid hormone). In the non-breeding season (April), the levels of endocrine regulation factors showed increasing trends in accordance with bodyweight gaining; nevertheless, the oocytes were growth phase belongs to almost peri-nucleous stages in all groups. In the breeding season (June), the levels of endocrine regulation factors were fluctuated that decreases in levels of sbGnRH and $FSH{\beta}$ mRNA expressions along with serum $E_2$ concentrations in 3 kg of group. However, $LH{\beta}$ mRNA expression levels sustained increasing trends by the bodyweight. Moreover, the oocytes developed that 2 kg and 3 kg groups obtained plentiful vitellogenic oocytes while 1 kg group was still composed with greater part of pre-vitellogenic oocytes. Especially, the oocytes of 3 kg group reached over 450 ${\mu}m$ of diameters that indicating possibility to enter the final maturations. These results suggest that the progress of pubertal development in female E. bruneus could be classify into three phases via bodyweight, including pre-puberty (1 kg), early-puberty (2 kg) and puberty (3 kg).

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.16 no.5
• /
• pp.888-892
• /
• 2002

Nae-Kyung says the puberty is corresponded to the age of 16～24(male) and 14～21 (female). And that time they are promoted the growth. However, Kidney qi doesn't make average situation during that time. So, the function of five viscera and six entrails fails to be perfect and symptoms appear. I came to the conclusion through the survey of about 200 high school students(male and female) and the theory of oriental medicine the distinctive features (like migraine, amnesia, depression, dysphoria, inappetence, irregular menstruation) came out that time. I defined this distinctive symptoms in boys and girls at puberty ‘synthetic symptoms of puberty’. For the medical cure and prevention I prescribed ‘Sachun-Nyung’ and that has medical benefits for ‘Replenishing qi and relieving the spleen, Soothing the liver and promoting blood circulation’

• The Journal of Korean Obstetrics and Gynecology
• /
• v.30 no.3
• /
• pp.20-28
• /
• 2017

Objectives: This review aims to report the efficacy of Oriental herbal medicine for Female Idiopathic Precocious Puberty Methods: We searched clinical study about precocious puberty from Pubmed, OASIS, Korea Traditional Knowledge Portal and National Assembly Library up to July 2017. Results: Four case reports have been identified. Six cases in total were found. And in the four cases where estradiol (E2) levels were above the normal levels in pre-treatment, the figures dropped to the normal levels in post-treatment. In the three cases with breast development and breast pain in pre-treatment, symptoms improved after the treatment. And, the sustained growth of height was reported in the four cases with the treatment duration of 30 days or more. Conclusions: It has been identified that oriental medicine assisted improvements of hormone levels and breast pain and growth of height on patients with precocious puberty, yet more case reports and well-designed studies would be necessary to guide better oriental herbal medicine treatment of precocious puberty.