• Journal of Genetic Medicine
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• 제17권1호
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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.

• Perspectives in Nursing Science
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• 제2권1호
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• pp.61-75
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• 2005

Physical and psychological events can produce stress response in various degrees. Stress affects many aspects of physiology including both brain and peripheral elements which is represented as hypothalamus-pituitary-adrenal axis. Brain elements consist of corticotropin-releasing hormone(CRH), locus ceruleus(LC)-norepinephrine(NE)/autonomic system. Peripheral elements include pituitary-adrenal axis and the autonomic nervous system, which coordinate the stress response. Current trend of the stress researches is emphasizing the mechanisms of the stress response which is adaptive or become maladaptive. This review introduces 1) the concepts of stress, 2) physiological and behavioral aspects of stress responses, 3) the consequences of stress response, 4) the measurements of stress and 5) stress management for those interested in stress research.

• Journal of Acupuncture Research
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• 제20권5호
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• pp.172-186
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• 2003

Acupuncture therapy has demonstrated efficacy in several clinical areas, and of these areas the understanding of pain has progressed immensely in the last two decades. The underlying mechanisms of acupuncture in general and the analgesic effect in particular are still not clearly delineated. The leading hypothesis include the effects of local stimulation, neuronal gating, release of endogenous opiates, and the placebo effect. Accumulating evidence suggests that the central nervous system(CNS) is essential for the processing of these effects, via its modulation of the autonomic nervous system, neuro-immune system, and hormonal regulation. These processes tap into basic survival mechanisms. As such, understanding the effects of acupuncture within a neuroscience-based framework becomes vital. We propose a model which incorporates the stress-induced hypothalamus-pituitary-adrenal axis(HPA-axis) model of Akil et al., the cholinergic anti-inflamatory observations of Tracey et al., and Petrovic et al.

• Biomolecules & Therapeutics
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• 제21권4호
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• pp.313-322
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• 2013

Previous studies have demonstrated that repeated administration of the exogenous stress hormone corticosterone (CORT) induces dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis and results in depression and anxiety. The current study sought to verify the impact of catechin (CTN) administration on chronic CORT-induced behavioral alterations using the forced swimming test (FST) and the elevated plus maze (EPM) test. Additionally, the effects of CTN on central noradrenergic systems were examined by observing changes in neuronal tyrosine hydroxylase (TH) immunoreactivity in rat brains. Male rats received 10, 20, or 40 mg/kg CTN (i.p.) 1 h prior to a daily injection of CORT for 21 consecutive days. The activation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily CTN administration significantly decreased immobility in the FST, increased open-arm exploration in the EPM test, and significantly blocked increases of TH expression in the locus coeruleus (LC). It also significantly enhanced the total number of line crossing in the open-field test (OFT), while individual differences in locomotor activities between experimental groups were not observed in the OFT. Taken together, these findings indicate that the administration of CTN prior to high-dose exogenous CORT significantly improves helpless behaviors, possibly by modulating the central noradrenergic system in rats. Therefore, CTN may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression and anxiety disorders.

• Archives of Pharmacal Research
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• 제27권8호
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• pp.863-866
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• 2004

The effect of substance P (Sub P) injected intrathecally (I.t.) on c-fos mRNA expression in vari-ous tissues was examined in the present study. We found that a single administration of Sub P(0.5 nM) caused an increase of the c-fos mRNA level in the hypothalamic-pituitary-adrenal(HPA) axis, hippocampus, and spinal cord. The time-course study showed that c-fos mRNA level was maximal at 10 min and began to decrease 30 min after the Sub P injection in all tis-sues, and the Sub P-induced increase of the c-fos mRNA level was returned to the control level 1 h after the injection. The kinetics of the c-fos mRNA expression in mice that were repeatedly injected with Sub P (every 30 min interval up to 4 times) were different in the HPA axis, hippocampus, and spinal cord. The increased c-fos mRNA level in the hypothalamus and the spinal cord induced by I.t. injected Sub P remained at a high level. In the pituitary gland, adrenal gland, and hippocampus, the increased level of c-fos mRNA expression gradually returned to the control level during the repeated substance P injections up to 4 times. Our results suggest that spinally injected Sub P-induced pain stress increases c-fos mRNA expres-sion in the spinal cord, hippocampus, and HPA axis. In mice repeatedly injected with Sub P, the kinetics of c-fos mRNA appear to be different varied from tissue to tissue.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1998년도 Advances in Ginseng Research - Proceedings of the 7th International Symposium on Ginseng -
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• pp.83-89
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• 1998

Ginseng total saponins (GTS) injected intracerebroventricularly (i.c.v.) at doses from 0.1-1 vs inhibited the i.c.v. injection stress-induced plasma corticosterone levels in mice. The inhibitory action of GTS was blocked by co-administered NG-nitro-L-arginine methyl ester (L-NAME; 1.5 us, i.c.v.), an. inhibitor of nitric oxide synthase (NOS). Of the ginsenosides Rbl, Rba, Rc, Rd, Re, Rf, Rgl,20(S)-Rg3, and 20(R)-Rg3 injected i.c.v. at doses from 0.01 to 0.3ug(or 1 uE),20(5)-Rg3 and Rc significantly inhibited the o.c.v. injection stress-induced Plasma corticosterone levels. The inhibitory actions of 20(S)-Rg3 and Rc were blocked by co-administered L-NAME (1.5 n, i.c.v.). These results suggest that G75, 20(S)-Rg3 and Rc may inhibit the i.c.v. injection stress-induced hypothalamo-pituitary-adrenal response by inducing NO production in the brain.

• 정신신체의학
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• 제4권1호
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• pp.146-154
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• 1996

스트레스와 면역기능 간의 관계는 중추신경계, 신경내분비계 및 면역계 간의 의사소통 즉 상호작용에 의해 이루어지고 있다. 중추신경계와 면역계가 상호작용하는 주요 경로는 임파조직의 신경계 wiring system과 신경내분비계다. 면역계는 neuropeptide를 생성하고 이것은 면역반응을 조절한다. 정신사회적 인자와 면역기능 간의 중개자로는 뇌하수체에서 방출되는 peptide, hormone 및 자율신경계 물질이 있다. 시상하부는 내분비계, 신경계 및 면역계를 통합하는 역활을 한다. 특히 시상하부의 paraventricular nucleus가 이 일에 중추적인 역할을 담당한다. 한편 내분비계는 면역계에 의해서 휘이드백을 받는다. 뇌하수체가 면역계를 조절하는 주요 경로로는 시상하부-뇌하수체-부신-흉선축, 시상하부-뇌하수체-성선-흉선축, 송과선-시상하부-뇌하수체축 등이 시사되고 있다. 스트레스와 면역계 간에는 양 방향의 경로가 있는 것으로 가정된다. 즉 스트레스가 면역계에 영향을 미칠 뿐만 아니라 면역계가 정신사회적 기능에 영향을 미칠 수 있다. 따라서 스트레스와 면역기능 간의 관계를 규명하기 위해서는 면역계, 내분비계, 자율신경계 및 뇌활동을 동시에 측정, 비교하여 이들을 통합할 필요가 있다.

• 한국발생생물학회지:발생과생식
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• 제6권2호
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• pp.117-122
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• 2002

포유동물에서 뇌와 부신에서 합성ㆍ분비되는 카테콜아민(Catecholamine, CA)계 신경전달물질인 dopamine(DA), norepinephrine(NE), epinephrine(E)은 체내 각종 생리현상의 조절에 필수적이며, 생식과 관련된 기능으로는 시상하부와 뇌하수체 사이의 GnRH-gonadotropin 호르몬 축의 활성을 조절함 외에도 번식과 연관된 여러 행동양식을 조절함이 잘 알려져 있다. 본 연구는 카테콜아민 생합성 효소인 tyrosine hydroxylase(TH), dopamine $\beta$ -hydroxylase(DBH), phenylethaolamine-N-methyl transferase(PNMT)의 유전자 발현에 영향을 미치는 sex steroid의 영향을 조사하였다. 성숙한 암컷 흰쥐의 난소를 제거(ovariectomy, OVX)하고 1주 경과 후 실험군과 대조군에 각각 17$\beta$-estradiol(E$_2$; 500$\mu\textrm{g}$/m1)이 들어 있는 silastic capsule과 sesame oil이 들어 있는 silastic capsule을 이식시키고 48시간 후에 희생시켰다. 채취된 조직에서 mRNA를 추출한 후 semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR)을 시행하였다. 그 결과로 (i) TH의 발현 정도는 OVX＋Oil군에서는 시상하부 > Substantia nigra(SNc) > 부신 순으로, OVX＋E$_2$군에서는 SNc ) 시상하부 > 부신 순으로 나타났다. TH발현에 미치는 estradiol의 효과로 SNc와 부신에서는 유의한 증가를 보인데 비해 시상하부에서는 유의한 감소를 관찰하였다. (ⅱ) DBH 발현 정도는 OVX＋Oil군과 OVXi＋E$_2$군에서 모두 부신 > SNc > 시상하부 순으로 나타났다. DBH 발현에 미치는 estradiol의 효과로 SNc에서는 유의한 감소를, 부신에서는 유의한 증가를, 그리고 시상하부에서는 감소하였으나 통계적 유의성이 없었다. (ⅲ) PNMT의 발현의 경우 SNc와 시상하부에서는 이미 알려진 바와 같이 alternative splicing에 의해 110bp 차이의 크고 작은 두 형태의 cDNA(PNMT과 PNMTSs가 증폭되었으나 부신에서는 작은 cDNA(PNMTs)만이 관찰되었다. PNMT1의 발현은 SNc가 시상하부보다 다소 높은 경향이었으나 유의성이 없었고, PNMTs의 발현정도는 OVX＋Oil군과 OVX＋E$_2$군 모두에서 부신 > SNC >시상하부 순으로 나타났다. PNMTs 발현에 미치는 estradiol의 효과로 SNc에서는 유의한 감소를, 부신에서는 유의한 증가를, 그리고 시상하부에서는 통계적 유의성은 없으나 증가하는 경향을 보였다. 본 연구에서는 카테콜아민 생합성 효소들의 유전자 발현의 조절에 미치는 estrogen의 영향이 세포기원이 neural crest cell인 부신 수질은 물론 뇌의 상이한 지역간에서도 조직특이적임을 관찰하였다. 이러한 결과는 각 조직에서의 estrogen 수용체 유형의 차이, 작용 모드와 각 효소 유전자 발현 사이에 중요한 상관관계가 있음을 시사한다.

• The Korean Journal of Physiology and Pharmacology
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• 제17권5호
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• pp.393-403
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• 2013

Baicalein (BA), a plant-derived active flavonoid present in the root of Scutellaria baicalensis, has been widely used for the treatment of stress-related neuropsychiatric disorders including depression. Previous studies have demonstrated that repeated restraint stress disrupts the activity of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depression. The behavioral and neurochemical basis of the BA effect on depression remain unclear. The present study used the forced swimming test (FST) and changes in brain neurotransmitter levels to confirm the impact of BA on repeated restraint stress-induced behavioral and neurochemical changes in rats. Male rats received 10, 20, or 40 mg/kg BA (i.p.) 30 min prior to daily exposure to repeated restraint stress (2 h/day) for 14 days. Activation of the HPA axis in response to repeated restraint stress was confirmed by measuring serum corticosterone levels and the expression of corticotrophin-releasing factor in the hypothalamus. Daily BA administration significantly decreased the duration of immobility in the FST, increased sucrose consumption, and restored the stress-related decreases in dopamine concentrations in the hippocampus to near normal levels. BA significantly inhibited the stress-induced decrease in neuronal tyrosine hydroxylase immunoreactivity in the ventral tegmental area and the expression of brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. Taken together, these findings indicate that administration of BA prior to the repeated restraint stress significantly improves helpless behaviors and depressive symptoms, possibly by preventing the decrease in dopamine and BDNF expression. Thus, BA may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression.

• Journal of Yeungnam Medical Science
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• 제38권1호
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• pp.60-64
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• 2021

Cushing syndrome (CS) is rare in pregnancy, and few cases have been reported to date. Women with untreated CS rarely become pregnant because of the ovulatory dysfunction induced by hypercortisolism. It is difficult to diagnose CS in pregnancy because of its very low incidence, the overlap between the clinical signs of hypercortisolism and the physiological changes that occur during pregnancy and the changes in hypothalamus-pituitary-adrenal axis activity that occur during pregnancy and limit the value of standard diagnostic testing. However, CS in pregnancy is associated with poor maternal and fetal outcomes; therefore, its early diagnosis and treatment are important. Here, we report two patients with CS that was not diagnosed during pregnancy, in whom maternal and fetal morbidity developed because of hypercortisolism.