• 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.

• Molecules and Cells
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• v.23 no.1
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• pp.88-93
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• 2007

Neuropeptide Y (NPY) is an orexigenic and hypothermic peptide. To understand its role in hypothermic conditions, male rats were placed in a $24^{\circ}C$ or $4^{\circ}C$ air chamber for 1.5 h. The expression of c-Fos protein, and NPY mRNA and protein, was analyzed in the hypothalamus 1 h-2 h later. The cold treatment increased the number of c-Fos-immunoreactive cells in the paraventricular hypothalamic nucleus (PVN) and arcuate nucleus (ARC). At the same time it decreased the density of NPY-immunoreactive components in the PVN, dorsomedial hypothalamic nucleus and ARC, as well as of NPY transcripts in the PVN and ARC. No colocalization of c-Fos with NPY was detected. These results suggest that short-term cold exposure should reduce indirectly NPY production in some hypothalamic nuclei to facilitate thermogenesis without inducing feeding behavior.

• The Journal of Korean Medicine
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• v.27 no.4
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• pp.191-197
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• 2006

Objectives : The aim of this study was to evaluate the anti-depressant effect of Chilbokum on rats under the forced swimming test (FST) Methods : The rats were treated with the herbal extract, Chilbokum. In order to induce depression-like symptoms, the FST was conducted afterwards. The immobility time was measured during a 5-min experimental session. The alterations of the 5-HT level in the hypothalamus and hippocampus and the change of corticosterone level in the blood induced by FST were determined in the rats. Results : The results were as follows: 1. The immobility time during 5 min of FST in the drug administration group showed significant decreases compared with the control group (p<0.05). 2. The FST+Chilbokum group had significantly increased 5-HT levels of the hypothalamus and hippocampus, compared with the control group (p<0.05, respectively). 3. The FST+Chilbokum group had significantly decreased corticosterone levels, compared with the control group (p<0.05). Conclusions : These results demonstrate that the reduced immobility time by Chilbokum may be mediated by the increase in 5-HT level in the hypothalamus and hippocampus, suggesting that Chilbokum has a potential therapeutic efficacy for human depression.

• Journal of Nutrition and Health
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• v.34 no.7
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• pp.727-733
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• 2001

The present study was conducted to identify the mechanism about the regulation of appetite by examining the expression patterns of neuropeptide Y in the hypothalamus of mice either fasting mouse for 24 hours or with anorexia mutant mouse. In order to investigate the patterns of expression of neurpeptide Y, immunohistochemistry was employed for measurements at the tissue level, along with the molecular biological techniques of reverse transcription polymerase chain reaction(RT-PCR) and dot blotting. The results of this study are as follows. The level of expression of neruopeptide Y, a neuropeptide known to enhance appetite, was shown to be lowered in the arcuate nucleus(ARC), paraventricular nucleus(PVN), lateral hypothalamic area(LHA), and dorsomedial hypothalamic nucleus(DMN) in both the fasting and anorexia mutant groups when measured via immunohistochemistry, a tissue-level method. RT-PCR and dot blotting, the molecular biological methods employed in this study, revealed that the level of neuropeptide Y mRNA in the entire hypothalamus was similar in the control and fasting groups and lower in the anorexia mutant group. The results of the present study showed that while the levels of expression of the neuropeptide Y in the various hypothalamic regions studied did not exhibit regular increases or decreases when measured immunohistochemically. But the entire hypothalamus via molecular biological methods showed that the changes in these levels were more definite in the anorexia mutant group than in the fasting group.

• Archives of Pharmacal Research
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• v.25 no.3
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• pp.343-348
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• 2002

Carbon monoxide (CO) are produced by heme oxygenase (HO), and HO was detected in hypothalamus. However, the roles of CO produced in hypothalamus was not fully elucidated. So, we tested the effects of CO on body temperature because preoptic-anterior hypothalamus was known as the presumptive primary fever-producing site. CO-saturated aCSF ($4{\;}{\mu}l$, i.c.v.) and hemin ($10{\;}{\mu}g$, i.c.v.) elicited marked febrile response. Pretreatment with indomethacin completely inhibited CO- and hemin-induced fever. Zinc protoporphyrin-IX ($10{\;}{\mu}g$, i.c.v.) or ODQ ($50{\;}{\mu}g$, i.c.v.) partially reduced hemin-induced febrile response. Dibutyryl-cGMP ($100{\;}{\mu}g$, i.c.v.) produced profound febrile response and this febrile response was attenuated by indomethacin. These results indicate that endogenous CO may have a role as a pyrogenic mediator in CNS and CO-mediated pyresis is dependent on prostaglandin production and partially on activation of soluble guanylate cyclase.

• The Journal of Internal Korean Medicine
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• v.19 no.1
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• pp.185-201
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• 1998

The present experiment was desined to examine catecholamines, 5-hydroxytryptamine, amino acids, malondialdehyde(MDA) and free radical scavening activity, by administering Samultang extract of a variety of concentraction to senile brain The results were summarized as followings: 1. Samultang significantly increased noradrenaline in the cortex, striatum, hippocampus and hypothalamus of the brain tissue of senile rats, and even though Samultang increased noradrenaline also in other brain tissue, there was no significance. 2. Samultang had effects on dopamine changes in hypothalamus of the brain tissue of senile rats. 3. Samultang significantly increased 5-hydrotryptamine in pons-medulla oblongota and cerebellum, but decreased in hypothalamus. 4. Samultang increased amino acid in the brain tissue of senile rats. 5. Samultang significantly decresed lipid peroxide production in the brain tissue of senile rats. 6. Samultang significantly decresed MDA and free radical in the brain tissue of senile rats. According to the above results, Samultang is assumed to improve brain function by reacting on biochemical of the senile brain, and that Samultang can be used to treat regressive brain disease carrying symptoms of psychoactive disorders.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.6
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• pp.467-477
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• 2001

We examined astrocyte regional heterogeneity in their morphological changes in response to various stimuli. Astrocytes were cultured from six different neonatal rat brain regions including cerebral cortex, hippocampus, cerebellum, mid brain, brain stem and hypothalamus. Astrocyte stellation was induced by serum deprivation and the maximum stellation in different regional astrocytes was achieved after 2 h. After 24 h, in all astrocyte cultures, the level of stellation returned to their original level. Cerebellar or hypothalamic astrocytes were the most or the least sensitive, respectively, to serum deprivation. The order of maximum sensitivity to serum deprivation among different regional astrocytes was: cerebellum＞mid $brain{\ge}hippocampus,\;brain\;stem{\ge}cerebral$ cortex＞hypothalamus. Isoproterenol-induced astrocyte stellation was also examined in different regional astrocytes, and similar order of maximum sensitivity as in serum deprivation was observed. Next a possible developmental effect on astrocyte morphological changes was examined in cerebral cortex and cerebellum astrocytes cultured from postnatal day 1 (P1), P4 and P7 rat brains. A much higher sensitivity of cerebellum astrocytes to serum deprivation as well as isoproterenol treatment was consistently observed in P1, P4 and P7-derived astrocytes compared to cerebral cortex astrocytes. The present study demonstrates different regional astrocytes maintain different levels of morphological plasticity in vitro.

• The Korean Journal of Physiology
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• v.11 no.2
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• pp.23-31
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• 1977

It is Proposed in the Present study to investigate the effects of TTX intravenously or intrahypothalamically administered on the arterial blood pressure and respiration and also to explorc effect of intrahypothalamically administered TTX on the pressor responses to electrical stimulation in the hypothalamus. The results obtained are as follows; 1) The pressor responses to electrical stimulation in the hypothalamus were markedly reduced after administration of TTX. In the $0.01\;{\mu}g/kg$ of TTX administered group, the pressor responses were almost abolished in 6 minutes and there was no tendency toward recovery throughout the experiment. 2) In $0.01\;{\mu}g/kg$ of TTX administered group, the mean arterial blood pressure and heart rate-were gradually reduced while there was a transient increase in respiratory rate followed by slow recovery thereafter. On the other hand no changes in arterial blood pressure, heart rate an4 respiration were observed in $0.005\;{\mu}g/kg$ TTX administered group. 3) Following intravenous administration of $1\;{\mu}g/kg$ TTX, the arterial blood pressure and heart rate were slowly reduced by 60 minutes while no marked changes were found in respiration. From the results of present study it is strongly suggested that TTX exerts its depressant effect not only on peripheral nerves but also on central nervous system.

• The Journal of Internal Korean Medicine
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• v.18 no.2
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• pp.94-111
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• 1997

The present experiment was designed to examine catecholamines, serotonine, amino acids, malondialdehyde and free radical scavenging activity, by administering Yukmijihwangtang extract of a variety of concentraction to senile brain. The results were summarized as followings: 1. Yukmijihwangtang significantly increased noradrenaline in the striatum, hypothalamus, midbrain and pons-medulla oblongota of the brain tissue of senile rats, and even though Yukmijihwangtang increased noradrenaline also in other brain tissue, there was no significance. 2. Yukmijihwangtang significantly increased dopamine in the striatum, hypothalamus and midbrain of the brain tissue of senile rats, and even though Yukmijihwangtang increased dopamine also in other brain tissue, there was no significance. 3. Yukmijihwangtang significantly increased serotonine in the pons- medulla oblongata and cerebellum of the brain tissue of senile rats, and even though Yukmijihwangtang increased serotonine also in the other brain tissue except hypothalamus and midbrain, there was no significance. 4. Yukmijihwangtang significantly increased amino acid in the brain tissue of senile rats. 5. Yukmijihwangtang significantly decresed malondialdehyde and free radical in the brain tissue of senile rats. According to the above results, Yukmijihwangtang is assumed to improve brain function by reacting on biochemical of the senile brain, and that Yukmijihwangtang can be used to treat regressive brain disease carrying symptoms of psychoactive disorders.

• Journal of Genetic Medicine
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• v.17 no.1
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• pp.1-10
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• 2020

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women, which is characterized by the oligo/anovulation, hyperandrogenism (HA) and polycystic ovarian morphology which are diagnostic criteria. PCOS has diverse clinical aspects in addition to those diagnostic criteria including increased risk for cardiovascular diseases, metabolic syndrome, dyslipidemia, type 2 diabetes and impaired fertility. Because of the heterogeneity of the disease, the pathogenesis of the disease has not been elucidated yet. Therefore, there is no cure for the endocrinopathy. HA and insulin resistance (IR) has been considered two major pillars of the pathogenesis of PCOS. Recent advances in animal studies revealed the critical role of neuroendocrine abnormalities in developing PCOS. Several pathways related to neuroendocrine origin have been investigated such as hypothalamus pituitary ovarian axis, hypothalamus pituitary adrenal axis and hypothalamus pituitary adipose axis. This review summarizes the current knowledge about the role of HA and IR in developing PCOS. In addition, we review the results of recent genome wide association studies for PCOS. This new perspective improves our understanding of the role of neuroendocrine origins in PCOS and suggest a novel potential therapeutic target for the treatment of PCOS.