• 한국수산과학회지
• /
• 제55권1호
• /
• pp.17-22
• /
• 2022

Successful reproduction in vertebrates necessitates complex interactions along the brain-pituitary-gonad axis, it is determined by gonadotropin releasing hormone produced in the hypothalamus of the brain, gonadotropin synthesized in the pituitary gland, and sex hormone secreted by the gonads. The goal of this study was to secure and test technology for controlling (inhibiting) sexual maturation hormones such as maturation hormones through hormone regulation. We studied the effect on sexual maturation of zebrafish Danio rerio by tamoxifen, anastrozole, exemestane and dopamine 4 kinds of sexual maturation inhibitors to feed and after administration. As a result, 4 kinds of sexual maturation inducing substances were mixed with zebrafish feed, it could be concluded that all of them were effective in inhibiting sexual maturation by reducing mRNA levels of genetic materials related to sexual maturation.

• The Korean Journal of Physiology and Pharmacology
• /
• 제17권5호
• /
• pp.393-403
• /
• 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
• /
• 제38권1호
• /
• pp.60-64
• /
• 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.

• 한국발생생물학회지:발생과생식
• /
• 제13권4호
• /
• pp.257-264
• /
• 2009

6-hydroxydopamine(6-OHDA)는 파킨슨 질환 동물 모델의 제조에 널리 사용되는 신경독소로 도파민성 뉴런에 대한 특이적인 독성을 나타낸다. 도파민 신호는 중추신경계의 광범위한 영역에서 생리 기능을 조절하는데, 이에 따라 파킨슨병 환자와 6-OHDA를 처리한 동물들의 신경내분비 활성에 극심한 변화가 있을 것으로 예상할 수 있다. 하지만 6-OHDA 주사 모델에서 시상하부-뇌하수체 신경내분비 회로에 관한 연구들은 전무한 실정이다. 본 연구는 6-OHDA에 의한 뇌 카테콜아민 합성의 차단이 성체 수컷 흰쥐의 시상하부-뇌하수체 호르몬 유전자들의 전사 활성에 일으키는 변화를 조사한 것이다. 생후 3개월의 수컷 흰쥐(SD strain)에 개체 당 $200{\mu}g$의 6-OHDA를 $10{\mu}\ell$의 생리식염수에 녹여 뇌실 내 주사(icv)하였고, 2주 후에 모든 실험동물들을 희생시켰다. 시상하부-뇌하수체 호르몬 유전자들의 mRNA 수준을 조사하기 위해 total RNA를 추출하여 반-정량적 RT-PCR을 시행하였다. 카테콜아민 생합성에서 속도조절효소로 작용하는 tyrosine hydroxylase(TH)의 경우 6-OHDA군에서 대조군에 비해 유의한 발현 감소가 나타났고(대조군:6-OHDA군=1:0.72${\pm}$0.02AU, p<0.001), 이를 통해 6-OHDA 주사의 효력을 확인 하였다. 시상하부에서 gonadotropin-releasing hormone(GnRH)과 corticotropin releasing hormone(CRH)의 mRNA 수준은 6-OHDA군이 대조군에 비해 유의하게 낮았다(GnRH, 대조군:6-OHDA군=1:0.39${\pm}$0.03AU, p<0.001; CRH, 대조군:6-OHDA군=1:0.76${\pm}$0.07AU, p<0.01). 뇌하수체에서 glycoprotein hormone들의 공통적인 alpha subunit(Cg$\alpha$)과 LH beta subunit(LH-$\beta$) 그리고 FSH beta subunit(FSH-$\beta$)의 mRNA 수준의 경우 모두 6-OHDA군에서 대조군에 비해 유의한 감소를 나타냈다(Cg$\alpha$, 대조군:6-OHDA군=1:0.81${\pm}$0.02AU, p<0.001; LH-$\beta$, 대조군:6-OHDA군=1:0.68${\pm}$0.04AU, p<0.001; FSH-$\beta$, 대조군:6-OHDA군=1:0.84${\pm}$0.05AU, p<0.01). 이와 유사하게, 6-OHDA군에서의 뇌하수체 adrenocorticotrophic hormone(ACTH) 전사 수준 역시 대조군에 비해 유의하게 낮았다(대조군:6-OHDA군=1:0.86${\pm}$0.04AU, p<0.01). 본 연구는 중추신경계로의 도파민 신경독소 주입에 의해 두 가지의 시상하부-뇌하수체 신경내분비 회로인 GnRH-성선자극호르몬 회로와 CRH-ACTH 회로의 전사 활성이 하향 조정됨을 증명하였다. 이러한 결과는 시상하부로의 CA 입력은 시상하부-뇌하수체 기능 조절을 통해 생식소와 부신의 활성에 영향을 미침을 시사하는 것으로, 파킨슨병 환자들에게서 빈번하게 발생하는 성 기능 장애와 열악한 스트레스 반응을 설명할 단서를 제공한다.

• Clinical Psychopharmacology and Neuroscience
• /
• 제16권4호
• /
• pp.422-433
• /
• 2018

Objective: Neuropsychiatric manifestations like depression and cognitive dysfunction commonly occur in inflammatory bowel disease (IBD). In the context of the brain-gut axis model, colitis can lead to alteration of brain function in a bottom-up manner. Here, the changes in the response of the hypothalamic-pituitary-adrenal axis and inflammation-related markers in the brain in colitis were studied. Methods: Dextran sodium sulfate (DSS) was used to generate a mouse model of colitis. Mice were treated with DSS for 3 or 7 days and sacrificed. We analyzed the gene expression of brain-derived neurotrophic factor (BDNF), cyclooxygenase 2 (COX-2), and glial fibrillary acidic protein (GFAP), and the expression of GFAP, in the hippocampus, hypothalamus, and amygdala. Additionally, the levels of C-reactive protein (CRP) and serum cortisol/corticosterone were measured. Results: Alteration of inflammatory-related markers varied depending on the brain region and exposure time. In the hippocampus, COX-2 mRNA, GFAP mRNA, and GFAP expression were upregulated during exposure to DSS. However, in the hypothalamus, COX-2 mRNA was upregulated only 3 days after treatment. In the amygdala, BDNF and COX-2 mRNAs were downregulated. CRP and corticosterone expression increased with DSS treatment at day 7. Conclusion: IBD could lead to neuroinflammation in a bottom-up manner, and this effect varied according to brain region. Stress-related hormones and serum inflammatory markers, such as CRP, were upregulated from the third day of DSS treatment. Therefore, early and active intervention is required to prevent psychological and behavioral changes caused by IBD, and region-specific studies can help understand the precise mechanisms by which IBD affects the brain.

• Journal of Microbiology and Biotechnology
• /
• 제22권3호
• /
• pp.422-430
• /
• 2012

Previous studies have demonstrated that repeated restraint stress in rodents produces increases in depression and anxiety-like behaviors and alters the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. The current study focused on the impact of Bupleurum falcatum (BF) extract administration on repeated restraint stress-induced behavioral responses using the forced swimming test (FST) and elevated plus maze (EPM) test. Immunohistochemical examinations of tyrosine hydroxylase (TH) expression in rat brain were also conducted. Male rats received daily doses of 20, 50, or 100 mg/kg (i.p.) BF extract for 15 days, 30 min prior to restraint stress (4 h/day). Hypothalamic-pituitary-adrenal axis activation in response to repeated restraint stress was confirmed base on serum corticosterone levels and CRF expression in the hypothalamus. Animals that were pre-treated with BF extract displayed significantly reduced immobility in the FST and increased open-arm exploration in the EPM test in comparison with controls. BF also blocked the increase in TH expression in the locus coeruleus of treated rats that experienced restraint stress. Together, these results demonstrate that BF extract administration prior to restraint stress significantly reduces depression and anxiety-like behaviors, possibly through central adrenergic mechanisms, and they suggest a role for BF extract in the treatment of depression and anxiety disorders.

• 한국발생생물학회지:발생과생식
• /
• 제16권1호
• /
• pp.31-38
• /
• 2012

Kisspeptin has been implicated in the process of puberty onset in various animal groups. This peptide is encoded by a gene, Kiss1 in avian and mammalian species. Contrary to these higher vertebrates, however, fish appeared to have another gene, Kiss2 that also codes for the precursor peptide of kisspeptin. To figure out biological significance of this gene during the puberty onset in fish, the expression profile of Kiss2 gene was investigated in the brain of Nile tilapia together with genes of GPR54, GnRH receptorI (rGnRHI) and GTH subunits ($LH{\beta}$ and $FSH{\beta}$). Expression of Kiss2 mRNA significantly increased at 2 weeks post hatch (wph) and 13 wph ($P$<0.05). This increase coincided with the increases of GPR54 and rGnRH I gene expression. Detection of $LH{\beta}$ and $FSH{\beta}$ subunit gene expression was possible later than 13 wph, indicating the activation of gonadotrophs in the pituitary. Data obtained from this study strongly suggest that, in addition to Kiss1 gene, Kiss2 gene is deeply associated with the onset of puberty by the activation of hypothalamus pituitary gonadal axis in Nile tilapia.

• 한국발생생물학회지:발생과생식
• /
• 제13권3호
• /
• 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.

• 대한추나의학회지
• /
• 제3권1호
• /
• pp.111-123
• /
• 2002

Objectives : There have been many studies of the effect of Bee Venom therapy about arthritis, but no one study was reported about its whole functional mechanism to musculo-skeletal system. This study was designed to investigate the effect, Indication, and side effect of Bee Venom therapy on musculo-skeletal disease by literature review of articles. Results : The effects of Bee Venom therapy to musculo-skeletal system are divided to Anti_inflammatory effect and Anti-nociceptive effect. Anti_inflammatory effect is achieved through competitive chemotaxis, immuno-regulation, increasing of cortisol secretion by stimulating hypothalamus-pituitary gland-adrenal cortex axis. Anti-nociceptive effect is achieved by Anti-inflammatory mechanism and it works similar to anti-nociceptive effect of the acupuncture acting on central and peripheral nociceptive transduction system. The Bee Venom therapy could cause severe side effect, for example, hypersensitivity and anaphylaxis, injury to central nerve system and cardiovascular system, peripheral blood system, and renal dysfunction. Conclusions : With its Anti-inflammatory and Anti-nociceptive mechanism, Bee Venom therapy is considered that has good effects to autoimmune disease, chronic inflammation of various musculo-skeletal disease and various pain syndrome. But the clinician must be careful for its side effects.

• The Korean Journal of Physiology and Pharmacology
• /
• 제3권2호
• /
• pp.215-222
• /
• 1999

Nonylphenol (NP) is a widespread environmental pollutant that has been shown to exert both toxic and estrogenic effects on mammalian cells. As the effects of NP on the reproductive system of adult male vertebrates are virtually unknown, we investigated not only the changes of reproductive hormone secretion in serum after chronic exposure to NP but also, in order to identify the site of its action, the reproductive hormone secretion in serum 48 hours after microinfusion of NP within hypothalamic preoptic area (POA). In the chronic exposure, the luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone in serum were decreased but prolactin (PRL) concentrations were increased. The LH, FSH, and testosterone in serum were decreased through the direct infusion of NP into POA, while there was no difference in mean serum prolactin between NP and control groups. These observations suggest that NP as endocrine disruptor has modulatory effects on hypothalamo-pituitary-gonadal axis and that the site of action of NP could be hypothalamic POA.