• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.65-65
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• 2003

Serotonin(5-hydroxytriptamine, 5-HT)은 biogenic amlne류 신경전달물질로써, 다양한 생리조절활성을 갖고있다. 생식과 관련된 5-HT 기능으로 최근 사정 기능의 조절 가능성이 제시되었는데, 항우울제로 흔히 사용되는 selective serotonin reuptake inhibitor(SSRI) 계 약물을 장기 투여할 때 Premature ejaculation이 개선된다는 임상적인 증거들이 보고되었다. 본 연구는 수컷 흰쥐를 사용하여 생식기관, 특히 사정과 관계되는 기관들에서의 5-HT 수용체 아형들의 유전자 발현 여부와 그 조절 기작을 조사하였다. 흰쥐 수컷의 생식장기들인 고환, 부정소, 정관, 정낭에서 사정현상에 관여하리라 추정되는 세로토닌 수용체 아형들(type 1A, 1B, 2C)의 유전자 발현을 RT-PCR과 Southern blot으로 확인하였다. SSRI(sertraline)을 흰쥐에 매일 투여하는 모델(25mg/개체, 2주간)에서 1A 아형의 발현의 경우 정낭에서는 감소하였으나 정관에서는 증가하였고, 1B 아형의 발현은 두 장기에서 공히 증가하였다. 고환 제거후 testosterone(T) 보충 실험 모델을 사용한 실험에서, 정낭에서의 1A와 1B 발현은 T 보충에 의해 감소하였고, 정관에서는 큰 변화가 없었다. 한편 고환, 정낭과 정관에서의 세로토닌 수용체 아형 1A와 1B의 발현은 사춘기의 개시와 함께 증가하였다가 이후 점차 감소하는 경향을 보였다. 본 연구 결과는 사정 현상에 있어서 말초성 세로토닌 시스템이 중요한 역할을 담당할 가능성을 시사하는 것으로써, (i) 고등 포유동물에서의 사정 기작의 조절에 대한 과학적인 이해를 증진시키고, (ⅱ) 세로토닌 수용체 아형간의 특이한 발현과 작용에 대한 이해를 통해 보다 효과적인 사정 부전 치료법 개발을 시도할 수있고, (ⅲ) ontogeny와 sex steroid 의존성에 관련된 연구 시도는 노화와 관련된 사정능력의 변화와 같은 남성과학 분야로의 접목을 기할 수 있다고 사료된다.

• Korean Journal of Biological Psychiatry
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• v.9 no.1
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• pp.3-7
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• 2002

Genes involved in the serotonin system are good candidates for the pathogenesis of mood disorder and mood-related disorders, such as eating disorder, obsessive-compulsive disorder, alcoholism, and suicide. Serotonin type 2A(5-HT2A) receptor gene promoter polymorphism(-1438A/G) has been reported. In this article, authors reviewed the literatures regarding association studies between -1438A/G and mood disorder and mood-related disorders. There are controversial results with limited data to date. Further researches on the -1438A/G in psychiatric disorders are required.

• Korean Journal of Biological Psychiatry
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• v.15 no.4
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• pp.303-309
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• 2008

Objectives : Some reports have suggested that 5-HT5A polymorphism allelic association was associated with depression, however, there has been no report about relationship between the 5-HT5A gene and antidepressant response. We conducted the association study of the 5-HT5A receptor gene polymorphisms (-19G/C,12A/T) and response to citalopram in Korean patients with major depressive disorder(MDD). Methods : A total of 106 patients with major depressive disorder were included in this study. The patient's symptoms were measured by 21-item Hamilton Depression Rating Scale(HAMD) at baseline, week 1, week 2, week 4 and week 8 during citalopram treatment. A Responder to citalopram was defined by 50% reduction of total HAMD scores. To analyze genetic polymorphisms, a polymerase chain reaction based method was used. Results : At week 8, responders were 62, non-responders were 44. No significant differences of genotypes or allelic association in 19G/C and 12A/T polymorphisms were observed between responsive and non-responsive patients. Conclusion : These results do not support the hypothesis that this polymorphism of the HT5A receptor gene is involved in the therapeutic response to citalopram.

• Development and Reproduction
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• v.6 no.2
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• pp.111-115
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• 2002

5-Hydroxytryptamine(5-HT; serotonin) system has been implicated in the modulation of male sexual behaviors and the secretion of reproductive hormones. In human males, selective serotonin re-uptake inhibitors(SSRIs) are known to improve the major male sexual dysfunction, premature ejaculation, through the central nervous system-mediated pathways. As numerous hormone and local factors, 5-HT may have peripheral role in the regulation of male sexual function. The expression of 5-HT receptor subtypes in the target tissue, however, has not been explored yet. The present study was undertaken to test whether the 5-HT receptor subtypes are expressed in the reproductive tissues of male rat, especially in ejaculatory machinery such as seminal vesicle and vas deferens. To do this, reverse transcription-polymerase chain reaction(RT-PCR) and Southern blot analysis were employed. The transcripts for the 1A, 1B and 2C subtypes of 5-HT receptor were amplified in all the tested tissues. The present study demonstrated the expression of 5-HT receptor in the rat ejaculatory machinery, suggesting that 5-HT may play a pivotal role in the male sexual function via not only central pathway but also peripheral route. Further study on the receptor subtype-specific effect and their harmonized mode of action will be needed to establish the understanding of ejaculation mechanism and drug design.

• Korean Journal of Biological Psychiatry
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• v.10 no.2
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• pp.133-140
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• 2003

Objective:Some candidate gene polymorphisms were reported to be associated with tardive dyskinesia (TD). The aim of this study was to investigate the association of the 5-$HT_{2A}$ receptor gene polymorphisms with TD in Korean schizophrenic subjects. Method:Subjects were of 59 schizophrenic patients with TD and 60 schizophrenic patients without TD for studying of 5-$HT_{2A}$ receptor gene polymorphisms. TD was evaluated using the Abnormal Involuntary Movement Scale(AIMS). Genomic DNA was amplified by PCR and digestion with MspI and BsmI. Result:There were no statistically significant differences in the demographic variables, such as age, male to female percentage, duration of illnesses and duration of antipsychotic drug exposure between the TD group and control group. 1) T102C polymorphisms and TD Comparing the TD group and control group, the 102T/C allele was associated with a significantly increased risk for TD (${\chi}^2$=5.560, df=1, p=0.018). 2) Three AIMS categories of TD and T102C genotype. There were statistically significant differences in the three AIMS categories(${\chi}^2$=6.835, df=2, p=0.033). Conclusion:These result suggest 102T/C genotypes of the 5-$HT_{2A}$ receptor gene are related to the development of TD. The 102T/C genotypes were associated with significantly higher AIMS orofacial dyskinesia scores. These findings suggest that the 5-$HT_{2A}$ receptor gene is significantly associated with susceptibility to TD in patients with chronic schizophrenia.

• Korean Journal of Biological Psychiatry
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• v.11 no.2
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• pp.146-154
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• 2004

Objective:Attention deficit hyperactivity disorder(ADHD) is the most common childhood psychiatric disorder, affecting 3-5% of school-aged children. Although the biological basis of ADHD is unknown, family studies provide strong evidence that ADHD has a genetic basis. Recent genetic studies have suggested associations between ADHD and serotonin 1B(5HT1B) receptor gene G861C polymorphism. The aim of this study is to test for the association between ADHD and 5HT1B receptor gene G861C polymorphism in Korean population. Method:We processed DNA extraction and genotyping. 106 Korean children with ADHD and their parents were analyzed using the transmission disequilibrium test(TDT) and haplotype-based haplotype relative risk (HHRR). And the ADHD children were compared with 212 age and gender matched normal controls. Results:There was no statistical difference of distributions between ADHD cases and controls. We did not observe any preferential transmission of alleles of 5HT1B receptor gene G861C polymorphism in ADHD. Conclusions:Though there is the possibility of failing to detect small genetic effects, our results show no evidence of an association between ADHD and 5HT1B receptor gene G861C polymorphism in the Korean population and indicate that it is unlikely that the 5HT1B receptor is implicated in the susceptibility to ADHD.

• Korean Journal of Biological Psychiatry
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• v.5 no.2
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• pp.215-218
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• 1998

The $5-HT_{2A}$ receptor is of great interest for research into schizophrenia and psychopharmacology in light of the observation that schizophrenic patients has 5-HT cortical-subcortical imbalance and atypical antipsychotic clozpine has $5-HT_{2A}$ antagonists properties. An significant association between schizophrenia and the T102C polymorphism of the gene for $5-HT_{2A}$receptor has been reported. In this study, we investigated an association between schizophrenia and the T102C polymorphism of the gene for $5-HT_{2A}$ receptor in Korean schizophrenic patients. The subjects consisted of 139 schizophrenic patients and 88 normal controls. Genomic DNA was amplified by PCR and digested with MsPI. The uncutt product identified allele 1(nucleotide sequence TCT) ; digested products of 216bp and 156bp identified allele 2(nucleotide sequence TCC). The allele frequencies and the genotypic distribution of $5-HT_{2A}$ receptor gene were not significantly different between schizophrenic patients and normal controls. Since allele frequencies of the T102C polymorphism may differ between individuals of different ethnic backgrounds, it needs to be conducted in an advanced research.