보고서 정보
주관연구기관 |
원광대학교 WonKwang University |
연구책임자 |
류도곤
|
발행국가 | 대한민국 |
언어 |
한국어
|
발행년월 | 1999-08 |
주관부처 |
보건복지부 |
사업 관리 기관 |
원광대학교 WonKwang University |
등록번호 |
TRKO200200054672 |
DB 구축일자 |
2013-04-18
|
초록
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현대사회가 문명의 발달로 복잡해지면서 사회생활에서의 정신적 stress, 환경오염물질에의 노출에 의한 성기능의 유지에 관련된 기관의 손상 등으로 성기능의 장애로 인한 의학적 및 사회적인 문제가 증가추세에 있다. 본 연구는 정상동물 및 성기능 저하 동물모델에서 성기능의 회복에 미치는 여러 한약재의 효과를 검사하고 성기능의 유지에 관련된 다양한 기전 즉 성기능 행동, 발기, 정자형성, 남성호르몬 합성효소의 활성, 분해, 세포내 수용체와의 친화력, estrogen, androgen-dependent cell에서 한약재가 미치는 효과를 구
현대사회가 문명의 발달로 복잡해지면서 사회생활에서의 정신적 stress, 환경오염물질에의 노출에 의한 성기능의 유지에 관련된 기관의 손상 등으로 성기능의 장애로 인한 의학적 및 사회적인 문제가 증가추세에 있다. 본 연구는 정상동물 및 성기능 저하 동물모델에서 성기능의 회복에 미치는 여러 한약재의 효과를 검사하고 성기능의 유지에 관련된 다양한 기전 즉 성기능 행동, 발기, 정자형성, 남성호르몬 합성효소의 활성, 분해, 세포내 수용체와의 친화력, estrogen, androgen-dependent cell에서 한약재가 미치는 효과를 구명하고자 본 실험을 수행하였다.
Abstract
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The present study was undertaken to evaluate the effects of several prescriptions of oriental medicine on sexual behavior, sperm function, serum androgen concentration, steriodogenetic functions of testis and testosterone metabolism of liver. Adult male Sprague Dawley rats maintained under standard
The present study was undertaken to evaluate the effects of several prescriptions of oriental medicine on sexual behavior, sperm function, serum androgen concentration, steriodogenetic functions of testis and testosterone metabolism of liver. Adult male Sprague Dawley rats maintained under standard laboratory conditions and were fed with the water extracts of Choakwiyeum (CY), Wookwiyeum (WY), Gamimajaojeunhwan (GH), Yeumyanggoakhaptosajahwan (YT), Gugissanghwatang (GT) and Sambojinheungdan (SD) for 4 weeks. To prevent steroidogenesis during the treatments of herb medicines, ketoconazole (100mg/kg/day) was administrated from Day 15 to Day 28, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was administrated in a single, oral dose of 20 μ g/kg on Day 15. All the treated animal along with the vehicle-treated controls were sacrificed 24 hrs after the last treatment of herb medicines. CY and GT are active in improving sexual functions(sexual behavior) at least in normal animals. Serum was assayed for the levels of testosterone (T), dihydrotestosterone (DHT), Luteinizing hormone (LH), and follicle stimulating hormone (FSH). CY elevated T concentration, while WY and YT decreased the concentration in serum from control rats. All prescriptions tested in this study were effective on elevating of T concentration from ketoconazole-treated rats. Especially, WY and GT treatments increased T concentration to 2.7- and 2.6-fold, respectively, relative to the concentration in rats treated with ketoconazole only. TCDD decreased serum T and DHT levels by 89% and 49%, respectively, from control values while SD treatment showed a significant protection against TCDD adminstration. However, there were no significant change in the concentrations of LH and FSH upon the treatments of 6 kinds of herb medicines, TCDD and ketoconazole. To analysis how several prescriptions of herb medicines increase serum T level in control and antiandrogen treated rats, the metabolic rates of T in liver and testicular steroidogenic activity were checked. Hepatic cytochrome P450 (P450) have been shown to exhibit unique patterns of T hydroxylation. Hydroxytestosterone (HT) metabolite patterns can be useful in monitoring the relative activities of individual P450 forms present in liver. We developed a reproducible and very excellent high performance liquid chromatography (HPLC) method for quantification of HT metabolites. More than 14 metabolites were separated as a single peak in chromatogram. Surprisingly, the formations of 16α-HT, 2α-HT, 16β-HT and 4-androstan-3,17-dione were reduced rapidly during TCDD treatment. The peaks of 15β-HT, 6β-HT and 2β-HT which are formed by P450 3A activity were reduced more slowly. These TCDD effects on the formation of hydroxytestosterones by P450s are not reported yet. The peak of 7α-HT was induced up to 12.6-fold at 336 hrs of TCDD treatment. P450 2A1 should be induced by TCDD because the enzyme is known to form 7α-HT, however this effect of TCDD is also not reported in any paper. Feeding of all prescriptions of herb medicines used in this study were not modified the activities of P450s in liver. Therefore herb medicines were not seemed to involve the catabolic processes of testosterone, ketoconazole and TCDD. Testicular P450scc which catalyzes the rate-limiting step for steroidogenesis was decreased significantly by the treatment of ketoconazole and TCDD. These decreases can be a reason for the reducing effects on serum T concentration by those chemicals. By the way, GH, CY and SD showed to increase P450scc activity to compared with the value in control although the differences were not significant statistically. In conclusion, these results suggest that feeding of some herb medicines can be useful to promote male sexual reproduction which is related with androgen and protect the the function against environmental contaminants, for example, endocrine disrupters.There has been increasing public and scientific concern that chemicals in the environment are affecting adversely on male reproductive capacities, for example, declines in sperm counts and concentration of androgens by disrupting normal hormone functions. In the present study, we tried to investigate whether we can protect the functions of endocrine disrupting chemicals on rat male reproductive system by the treatment of Oriental herb medicines. Most of the medicines are widely used in the prescription for the promoting of reproductive or sexual potentials. One part of this study was focusing on spermatogenesis, sexual behaviors and the proliferative responses related with the binding of sex hormones on their receptors. The other was on the synthesis of progesterone, 17α-OH progesterone, androstenedione or testosterone, and the catabolic metabolism of testosterone. Gagamchanyukdan(GD) was found to be effective in preventing 2,3,7,8-tetrachlorodibenzo -p-dioxin (TCDD)-induced sexual dysfunction, while Gojinyeumja(GJ), Yeunryunggobondan (YD) and HSA(Herba epimedii, Semen psoraleae, Aspongopus chinensis Dallas) stimulated sexual behaviors of normal rats. But those medicines didn't stimulate in sexually disabled animals by TCDD. All medicines didn't change sperm counts in normal and TCDD-treated rats. Using yeast based estrogen receptor assay, we have examined the inhibitory effects of some herb medicines on estrogen-like activities of bisphenol A and diethylstilbestrol. The water extracts of Placenta hominis, Scolpendrae, Raix astragali and GD inhibited the estrogen-like activities significantly. Placenta homisns, Batryticatus bombycis, Aspongopus chinensis Dallas stimulated the proliferative response of MCF-7 cell which is used as estrogen-screen assay. However, Rhizoma gastrodiae, Rhizoma arisaematis, Semen plantaginis, Radix salviae miltiorrhizae increased the proliferation of LNCap cell which is controled by androgen. Addition of Placenta homins and Batryticatus bombycis resulted in increases in respiration and progesterone output of I-10 and R2C Leydig cells. Hydroxytestosterone (HT) metabolites done by hepatic cytochrome P450 enzymes (P450) can be useful in monitoring the activities of some P450s. We developed a reproducible and very excellent HPLC method for quantification of HT metabolites. Fructus rubi inhibited the decomposing metabolism of testosterone except 16β-HT and Fructus torilis inhibited the synthesis of 6β-HT only. Testicular steroidogenic function was examined by a newly developed HPLC. analysis of several androgens formed by 17α-hydroxylase and 17β -hydroxysteroid dehydrogenase. Radix salviae miltiorrhizae and Semen plantagins increased the synthesis of androgens in both control and ketoconazole treated reactions. These ex vivo and in vitro results suggested that the water extracts of Radix salviae miltiorrhizae and 차전자 can be useful to promote the production of androgen in rat. In fact, these medicines increased significantly the plasma concentration of testosterone in adult male rat. Works are in progress to define what components from several extracts were involved the stimulation of androgen synthesis and others.
목차 Contents
- 제 1 장 서론...19
- 제 2 장 국내.외 기술개발 현황...21
- 제 3 장 연구개발수행 내용 및 결과...25
- 제 1 절 제 1 차년도-제 1 세부과제...25
- 1. 연구수행 내용...25
- 2. 시험군의 구성...26
- 3. 연구수행 방법...27
- 4. 연구결과...33
- 제 2 절 제 1 차년도-제 2 세부과제...43
- 1. 연구내용 및 방법...43
- 2. 연구결과...45
- 제 3 절 제 2 차년도-제 1 세부과제...58
- .정상 rat 및 성기능 억제제를 투여한 rat에서의 성기능 증진시험...58
- 1. 연구개발 수행내용...58
- 2. 연구수행 방법...61
- 3. 연구결과...63
- .Estrogen receptor binding 및 androgen receptor binding 연구...72
- 1. 재료...72
- 2. 방법...72
- 3. 결과...73
- .Estrogn-estrogen receptor complex에 의한 형질발현 연구...76
- 1. 재료 및 방법...76
- 2. 결과...80
- 제 4 절 2차년도-제 2 세부과제...87
- 1. 연구개발 수행내용...87
- 2. 연구개발 수행결과...89
- 제 4 장 연구개발목표 달성도 및 대외기여도...107
- 제 5 장 연구개발결과의 활용성과 및 계획...110
- 제 6 장 기타 중요변경사항...112
- 제 7 장 참고문헌...113
- 최종보고서 요약(초록)...119
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