• 한국수정란이식학회지
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• 제33권4호
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• pp.305-311
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• 2018

Gonadotropin releasing hormone (GnRH) centrally plays a role in control of the hypothalamic-pituitary-gonadal axis-related hormone secretions in the reproductive neuroendocrine system. In addition, hormone receptors like luteinizing hormone receptor (LHR) are important element for hormones to take effect in target organ. However, ageing-dependent changes in terms of the distribution of GnRH neurons in the brain and LHR expression in the acyclic ovary have not been fully understood yet. Therefore, we comparatively investigated those ageing-dependent changes using young (1-5 months), middle (11-14 months) and old (21-27 months) aged female mice. Whereas a number of GnRH positive fibers and neurons with monopolar or bipolar morphology were abundantly observed in the brain of the young and middle aged mice, a few GnRH positive neurons with multiple dendrites were observed in the old aged mice. In addition, acyclic ovary without repeated development and degeneration of the follicles was shown in the old aged mice than others. LHR expression was localized in theca cells, granulosa cell, corpora lutea and atretic follicle in the ovaries from young and middle aged mice, in contrast, old aged mice had few positive LHR expression on the follicles due to acyclic ovary. However, the whole protein level of LHR was higher in the ovary of old aged mice than others. These results are expected to be used as an important basis on the relationship between GnRH and LHR in old aged animals as well as in further research for reproduction failure.

• Anatomy and Cell Biology
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• 제56권1호
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• pp.69-85
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• 2023

Depression is one of the most common neuropsychiatric disorders and is associated with dysfunction of the neuroendocrine system and alterations in specific brain proteins. Boophone disticha (BD) is an indigenous psychoactive bulb that belongs to the Amaryllidacae family, which is widely used in Southern Africa to treat depression, with scientific evidence of potent antidepressant-like effects. The present study examined the antidepressant effects of BD and its mechanisms of action by measuring some behavioural parameters in the elevated plus maze, brain content of corticosterone, brain derived neurotropic factor (BDNF), and neuroblast differentiation in the hippocampus of Balb/c mice exposed to the five day repeated forced swim stress (5d-RFSS). Male Balb/c mice were subjected to the 5d-RFSS protocol to induce depressive-like behaviour (decreased swimming, increased floating, decreased open arm entry, decreased time spent in the open arms and decreased head dips in the elevated plus maze test) and treated with distilled water, fluoxetine and BD. BD treatment (10 mg/kg/p.o for 3 weeks) significantly attenuated the 5d-RFSS-induced behavioural abnormalities and the elevated serum corticosterone levels observed in stressed mice. Additionally, 5d-RFSS exposure significantly decreased the number of neuroblasts in the hippocampus and BDNF levels in the brain of Balb/c mice, while fluoxetine and BD treatment attenuated these changes. The antidepressant effects of BD were comparable to those of fluoxetine, but unlike fluoxetine, BD did not show any anxiogenic effects, suggesting better pharmacological functions. In conclusion, our study shows that BD exerted antidepressant-like effects in 5d-RFSS mice, mediated in part by normalizing brain corticosterone and BDNF levels.

• 정신신체의학
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• 제24권1호
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• pp.43-53
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• 2016

연구목적 심리외상에 노출된 이후 신체증상이 매우 빈번히 발생하곤 한다. 이러한 신체증상은 사회기능과 직업기능 및 환자-의사 관계와 종종 연관되지만 외상후스트레스장애 진단 범주에 포함되지 않은 상태이다. 본 논문에서는 이러한 신체증상의 기전, 흔한 임상양상, 그리고 치료에 대해 고찰하고자 한다. 방 법 PubMed, Scopus, Google Scholar, KoreaMed, KISS와 같은 학술검색엔진을 사용하여 2016년 3월 31일까지 검색된 심리외상 노출 이후 신체증상에 관한 자료를 바탕으로 연구하였다. 결 과 심리외상 노출 이후의 신체증상의 발생 기전은 심리적인 측면과 생리적인 측면으로 구분될 수 있었다. 심리기전은 정신역동이론, 인지행동이론, 그리고 다른 이론들이 포함되었다. 생리기전은 신경내분비 및 면역계, 자율신경계, 중추 신경계의 변화로 설명되었다. 심리외상과 연관된 신체증상은 두경부, 흉부, 복부, 기타 근골격계, 피부 및 면역계에서 나타나는 다양한 건강문제로 표현되었다. 이러한 신체증상의 표준화된 치료에 대한 연구는 매우 부족하였다. 결 론 임상의와 재난정신건강지원 실무자는 심리외상에 대한 개입이나 PTSD 치료 동안 동반된 신체증상에 대해 항상 염두에 두어야 한다. 심리외상과 PTSD에서 보이는 이러한 신체증상에 대해 더 많은 연구가 진행될 필요가 있다.

• Animal cells and systems
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• 제3권2호
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• pp.103-113
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• 1999

Many in-depth reviews related to regulations of prolactin secretion are available. We will, therefore, focus on controversial aspects using personal opinion in this review. The neuroendocrine control of prolactin secretion from the anterior pituitary gland involves multiple factors including prolactin-release inhibiting factor (PIF) and prolactin releasing factor (PRF). The PIF exerts a tonic inhibitory control in the physiological conditions. The PIF should be able to effectively inhibit prolactin release or a lifetime, but the inhibitory action of dopamine cannot be sustained for a long period of time. Perifusion of a high concentration of dopamine (l ,000 nM) could not sustain inhibitory action on prolactin release but when a small amount of ascorbic acid (0.1 mM) is added in a low concentration of dopamine (3 nM) solution, prolactin release was inhibited for a long period. Ascorbate is essential for dopamine action to inhibit prolactin release. We have, therefore, concluded that the PIF is dopamine plus ascorbate. The major transduction system for dopamine to inhibit prolactin release is the adenylyl cyclase system. Dopamine decreases cyclic AMP concentration by inhibiting adenylyl cyclase, and cyclic AMP stimulates prolactin release. However, the inhibitory mechanism of dopamine on prolactin release is much more complex than simple inhibition of CAMP production. The dopamine not only inhibits cyclic AMP synthesis but also inhibits prolactin release by acting on a link(s) after the CAMP event in a chain reaction for inhibiting prolactin release. Low concentrations of dopamine stimulate prolactin release. Lactotropes are made of several different subtypes of cells and several different dopamine receptors are found in pituitary. The inhibitory and stimulatory actions induced by dopamine can be generated by different subtype of receptors. The GH$_4$ZR$_7$ cells express only the short isoform (D$_{2s}$) of the dopamine receptor, as a result of transfecting the D$_{2s}$ receptors into GH$_4$C$_1$ cells which do not express any dopamine receptors. When dopamine stimulates or inhibits prolactin release in GH$_4$ZR$_7$ cells, it is clear that the dopamine should act on dopamine D$_{2s}$ receptors since there is no other dopamine receptor in the GH$_4$ZR$_7$. Dopamine is able to stimulate prolactin release in a relatively low concentration while it inhibits in a high concentration in GH$_4$ZR$_7$. These observations indicate that the dopamine D$_2$ receptor can activate stimulatory and/or inhibitory transduction system depending upon dopamine concentrations.

• 한국발생생물학회지:발생과생식
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• 제15권3호
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• pp.265-272
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• 2011

It is well known that adipose tissue or body fat has been proved as a crucial component of brain-peripheral axis which can modulate the activities of reproductive hormonal axis in female mammals including rodents and human. Concerning the male reproduction, however, the role of adipose tissue has not been thoroughly studied. The present study was carried out to elucidate the effect of a high-fat (HF) diet on the reproductive system of postpubertal male rats. The HF diet (45% energy from fat, HF group) was applied to male rats from week 8 after birth for 4 weeks. The blood glucose levels, body and tissue weights were measured. Histological studies were performed to assess the structural alterations in the reproductive tissues. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus and pituitary, total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Body weights (p<0.01) and blood glucose levels (p<0.01) of HF group were significantly higher than those of control animals. Similarly, the weights of epididymis (p<0.05), prostate (p<0.01), seminal vesicle (p<0.01) in HF group were higher than control levels. The weights of testis were not changed. The weights of kidney (p<0.001) and spleen (p<0.01) were significantly higher than control levels while the adrenal and pancreas weights were not changed. There were only slight alterations in the microstructures of accessory sex organs; the shape of luminal epithelial cells in epididymis from HF group were relatively thicker and bigger than those from control animals. In the semi-quantitative RT-PCR studies, the mRNA levels of hypothalamic GnRH (p<0.05) in HF group were significantly higher than those from the control animals. The mRNA levels of kisspeptin in HF group tend to be higher than control levels, the difference was not significant. Unlike the hypothalamic GnRH expression, the mRNA levels of pituitary $LH{\beta}$ and $FSH{\beta}$ were significantly decreased in HF group (p<0.05). The present study indicated that the 4-weeks feeding HF diet during the postpubertal period can alter the hypothalamus-pituitary (H-P) neuroendocrine reproductive system These results suggest that the increased body fat and the altered leptin input might disturb the H-P reproductive hormonal activities in male rats, and the changed activities seem to be responsible for the changes of tissue weights in accessory sex organs.

• 한국발생생물학회지:발생과생식
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• 제5권1호
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• pp.1-8
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• 2001

골든 햄스터의 생식활동은 광주기(하루 중 조명 시간)에 의해 결정된다. 광주기는 일년 동안 예측할 수 있는 환경요인이다. 주간 길이가 야간 길이보다 긴 여름에 햄스터의 생식 활동은 왕성하다. 생식 기능을 유지시키는 조명 시간은 하루에 적어도 12.5시간이다. 송과선을 제거시키면 광주기의 정보가 억제되기 때문에, 광주기의 정보는 송과선을 통하여 중재된다. 송과선을 제거 당한 핼스터는 생식 활동이 유지되고, 생식소 기능을 억제하는 상황에서도 생식 기능을 촉진시킨다. 송과선은 멜라토닌을 분비하고 멜라토닌은 광주기 정보를 반영 한다. 멜라토닌을 적절히 투입하면 송과선과 무관하게 생식소 퇴화가 유도된다. 생식체계를 기능적으로 통합하는 신경내분비 신호로 환경 정보가 전환하는 기전을 멜라토닌이 조절함을 시사한다. 광범위한 연구에도 불구하고, 멜라토닌의 작용부위는 알려지지 않았다. 이는 멜라토닌이 생식 호르몬의 분비에 미치는 즉각적인 효과가 없기 때문이다. 그러나, 성적으로 퇴화된 동물들은 생식 호르몬 수준이 낮고 시상하부 내 GnRH 양이 증가한다. 광주기 혹은 멜라토닌 처리가 생식 기능을 억제하는 효과는 GnRH 신경계에 의해 중재됨을 의미한다. 멜라토닌이 GnRH 신경에 미치는 작용 기전이 조사되어야 한다. 멜라토닌 수용체가 클로닝되어, 목적 조직에 미치는 멜라토닌의 작용 기전과 해부학적 위치를 통하여 멜라토닌의 다양하고 잠재적인 능력을 분자수준에서 연구하는데 공헌할 것이다.

• 한국동물학회지
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• 제39권4호
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• pp.337-351
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• 1996

멜라토닌은 대뇌와 소뇌 사이에 위치한 송과선에서 분비되는 호르몬으로 빛이 없는 밤에만 분비된다. 멜라토닌은 분자적 수준에서부터 개체의 행동에 이르기 까지 다양한 기능을 보인다. 특히, 생식에 미치는 영향은 광범위하여, 온대지방에 사는 대부분의 동물은 주위 환경에 적응하여 종족을 유지하는 유일한 계절적 번식을 한다. 햄스터의 생식활동은 여름에 왕성하고 겨울에 정지된다.이는 많은 환경요소중 광주기의 효과가 송과선에 의해 제거하면 광주기의 영향은 사라진다. 즉 생식에 미치는 광주기의 효과가 송과선에 의해 중재 됨을 의미한다. 또한 송과선 호르몬인 멜라토닌의 적절한 처리는 생식활동을 억제한다. 따라서 멜라토닌은 생식에 미치는 광주기의 정보를 생식내분비계로 전달하는 신경전달물질로 사료된다. 시상하부의 특정부위를 절제한 후 광주기나 멜라토닌을 처리하여 멜라토닌의 작용부위에 관한 연구가 되었으나 동물마다 차이점을 보인다. 대부부의 동물에서 공통적인 부위는 suprachiasmatic nuclei와 pars tuberalis이다. 멜라토닌이 생식에 미치는 작용기작은 아직 밝혀지지 않았다. 이는 멜라토닌의 지속적 처리가 멜라토닌의 장기적처리는 이들 호르몬의 분비를 저하시키고, 시상하부에서의 gonadotropin-releasing hormone (GnRH)양을 증가시킨다. 이 결과는 멜라토닌의 지속적인 처리가 시상하부로부터의 GnRH 양을 분비를 감소킴으로써 생식활동을 억제하는 것으로 사료된다.그러나, 멜라토닌에서 GnRH 신경까지의 정보전달은 아직 밝혀지지 않았다. Opioid 신경에 대한 광주기와 멜라토닌의 효과가 동일한 점은 opioid신경의 매개체 역할을 제시하고 있다. 최근에 멜라토닌 수용체가 개구리의 피부와 몇몇 동물의 뇌와 시세포에서 크로닝되었다. 이수용체는 G protein과 관련되고 cAMP 생성을 억제한다. 앞으로 이 멜라토닌 수용체의 존재여부와 분자생물학적 연구는 멜라토닌의 작용부위와 표적세포에서의 작용기작을 설명하는 데 크게 기여할 것으로 기대된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7039-7044
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• 2015

Background: Many functional molecules controlling diverse cellular function are included in low-molecular weight proteins and peptides. Materials and Methods: To identify proteins controlling function in lung adenocarcinomas (AC), we performed two-dimensional gel electrophoresis employing tricine-SDS polyacrylamide in the second dimension (tricine 2-DE). This system was able to detect proteins under 1 kDa even with post-translational modifications. To confirm the utility of detected proteins as novel tumor markers for AC, we performed immunohistochemical analysis using 170 formalin-fixed and paraffin-embedded lung AC tissues. Results: Tricine 2-DE revealed that five proteins including S100A16 were overexpressed in lung AC-derived cells compared with lung squamous cell carcinoma, small cell carcinoma, and large cell neuroendocrine carcinoma-derived cells. Immunohistochemically, S100A16 showed various subcellular localization in lung cancer tissues and a membranous staining status was correlated with the T-factor (P=0.0008), pathological stage (P=0.0015), differentiation extent (P=0.0001), lymphatic invasion (P=0.0007), vascular invasion (P=0.0001), pleural invasion (P=0.0087), and gender (P=0.039), but not with the age or smoking history. More importantly, membranous staining of S100A16 was significantly correlated with a poorer overall survival of either stage I (P=0.0088) or stage II / III (P=0.0003) lung AC patients, and multivariate analysis confirmed that membranous expression of S100A16 was an independent adverse prognostic indicator (P=0.0001). Conclusions: The present results suggest that S100A16 protein is a novel prognostic marker for lung AC.

• 대한약리학회지
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• 제23권2호
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• pp.57-75
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• 1987

Two modalities of gonadotropin secretion, pulsatile gonadotropin and preovulatory gonadotropin surge, have been identified in the mammals. Pulsatile gonadotropin secretion is modulated by the pulsatile pattern of GnRH release and complex ovarian steroid feedback actions. The neural mechansim that regulates the pulsatile release of GnRH in the hypothalamus is called "GnRH pulse generator". Ovarian steroids, estradiol and progesterone, appear to exert thier feedback effects both directly on the pituitary to modulate gonadotropin release and on a hypothalamic site to modulate GnRH release; estradiol primarily affects the amplitude while progesterone decreases the frequency of the pulsatile GnRH. Steroid hormones are known to affect catecholamine transmission in brain. MBH-POA is richly innervated by NE systems and close apposition of NE terminals and GnRH cell bodies occurs in the MBH as well as in the POA. NE normally facilitates pulsatile LH release by acting through ${\alpha}-receptor$ mechanism. However, precise nature of facilitative role of NE transmission in maintaining pulsatile LH has not been clearly understood. Close apposition of DA and GnRH terminals in ME might permit DA to influence GnRH release. Action of DA transmission probably is mediated by axo-axonic contacts between GnRH and DA fibers in the ME. Dopamine transmission does not normally regulate pulsatile LH release, but under certain conditions, increased DA transmission inhibit LH pulse. Endogenous opioid acts to suppress the secretion of GnRH into hypophysial portal circulation, thereby inhibiting gonadotropin secretion. However, an interaction between endogenenous opioid peptides and gonadotropin release is a complex one which involves ovarian hormones as well. LH secretion appears to be most suppressed by endogenenous opioids during the luteal phase, at a time of elevated progesterone secretion. The arcuate nucleus contains not only cell bodies for GnRH and ${\beta}-endorphin$ but also a dense aborization of fibers suggesting that GnRH release is changed by the interactions between GnRH and ${\beta}-endorphin$ cell bodies within the arcuate nucleus. The frequency and amplitude of pulsatile LH release seem to be increased during the preovulatory gonadotropin surge. Estradiol exerts positive feedback action on the hypothalamo-pituitary axis to trigger preovulatory LH surge. GnRH is also crucial hormonal stimulus for preovulatory LH surge. It is unlikely, however, that increased secretion of GnRH during the preovulatory gonadotropin surge represents an obligatory neural signal for generation of the LH discharge in primates including human. Modulation of preovulatory LH surge by catecholamines has been studied almost exclusively in rats. NE and E may be involved in distinct way to accumulate GnRH in the MBH and its release into the hypophysial portal system during the critical period for LH surge on proestrus in rats. However, the mechanisms whereby augmented adrenergic transmission may facilitate the formation and accumulation of GnRH in the ME-ARC nerve terminals before the LH surge have not been clearly understood.

• Applied Microscopy
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• 제40권4호
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• pp.211-218
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• 2010

포유동물의 난소는 호르몬과 감각신경 및 교감신경의 지배를 받아 난소 내 혈류의 조절, 스테로이드 호르몬 생성 및 난포의 발달과 관계된 난소의 고유기능이 조절되고 있다. 본 실험에서는 통상적인 추적자인 CT-HRP와 Pseudorabies바이러스(PRV)의 Bartha strain을 신경추적자로 이용하여 뇌하수체 후엽 및 난소와 연결된 중추신경부위를 밝히고자 하였다. 또 oxytocin을 난소 지배 신경축속에서 동정함으로써 신경축내 oxytocinergic neuron들의 존재를 확인하고, 이들이 배란을 중심으로 한 난소생식주기에 따라 보이는 중추 내 oxytocin신경세포의 변화를 조사하고자 하였다. Sprague-Dawley 흰쥐를 대상으로 난소 내에 PRV를 주사하고 48시간 후 실험동물들은 4% paraformaldehyde-lysine periodae로 고정하였으며, 뇌를 적출하여 $30{\mu}m$ 두께의 관상연속 절편을 만들어 CTHRP, PRV 및 oxytocin에 대한 삼중염색을 시행하였다. 본 실험 결과 후뇌에서부터 전뇌에 이르기까지 PRV에 양성반응을 보인 신경핵들이 관찰되어 난소를 지배하는 신경축을 구성할 수 있었다. 또 시상하부의 뇌실옆핵에서 oxytocin, PRV와 CT-HRP에 삼중으로 염색된 세포가 관찰됨으로써 신경내분비축과 자율신경축이 공동으로 기원하고 있다는 것을 형태학적으로 보여주었다. 따라서 oxytocin은 이 두 계통 내에서 호르몬의 역할과 신경전달물질의 역할을 겸할 것이라는 것을 추측할 수 있었다.