• 한국동물학회지
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• 제34권3호
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• pp.426-431
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• 1991

The present study examines the effect of naloxone, mu-opioid receptor antagonist, on prolactin (PRL) gene expression and secretion induced by estradiol (I) treahent in vivo. Adult rats were ovariectomized (OW) and implanted with Silastic capsules containing either vehicle (oil) or E. Three days later, NAL (2 mg/kg BW) or saline urere injected 30 min prior to sacrifice. To examine PRL secretion in vitro, the pituitaries were incubated in the superfusion system for 3 hrs. Superfusates were collected at 10 min intenrals on ice and subjected to PRL radioimmunoassay. Endogenous release of PRL in OU( + I rats was signifcantlv higher than that in OVX rats (mean $\pm$ SE; 24.5 $\pm$ 3.1 vs 14.5 $\pm$ 2.9 ns/10 min). A single injection of NAL clearly inhibited PRL release in Nitro from pituitaries derived from OW + I rats, but not from OW group. PRL myNA was determined by RNA-blot hybridisation assay with nicktranslated PRL CDNA. E stimulated PRL mRNA about 3 fold over that shown in OW group. Treahent of NAL suppressed the I-stimulated PRL myNA in OVX + I group, but not in OVX group. These data clearly showed that the NAL-induced inhibition of PRL secretion was well correlated with changes in PRL mRNA level and this inhibitory process appears to be mediated in I-dependent manner.

• Journal of Korean Neurosurgical Society
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• 제54권6호
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• pp.461-466
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• 2013

Objective : Although curcumin has a protective effect on bone remodeling, appropriate therapeutic concentrations of curcumin are not well known as therapeutic drugs for osteoporosis. The purpose of this study was to compare the bone sparing effect of treatment of low-dose and high-dose curcumin after ovariectomy in rats. Methods : Forty female Sprague-Dawley rats underwent either a sham operation (the sham group) or bilateral ovariectomy (OVX). The ovariectomized animals were randomly distributed among three groups; untreated OVX group, low-dose (10 mg/kg) curcumin administered group, and high-dose (50 mg/kg) curcumin group. At 4 and 8 weeks after surgery, serum biochemical markers of bone turnover were analyzed. Bone histomorphometric parameters of the 4th lumbar vertebrae were determined by micro-computed tomography (CT). In addition, mechanical strength was determined by a three-point bending test. Results : High-dose curcumin group showed significantly lower osteocalcin, alkaline phosphatase, and the telopeptide fragment of type I collagen C-terminus concentration at 4 and 8 weeks compared with the untreated OVX group as well as low-dose curcumin group. In the analyses of micro-CT scans of 4th lumbar vertebrae, the high-dose curcumin treated group showed a significant increase in bone mineral densities (p=0.028) and cortical bone mineral densities (p=0.036) compared with the low-dose curcumin treated group. Only high-dose curcumin treated group had a significant increase of mechanical strength compared with the untreated OVX group (p=0.015). Conclusion : The present study results demonstrat that a high-dose curcumin has therapeutic advantages over a low-dose curcumin of an antiresorptive effect on bone remodeling and improving bone mechanical strength.

• 대한수의학회지
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• 제44권2호
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• pp.171-177
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• 2004

The regional distributions and frequencies of argentaffin endocrine cells in gastrointestinal (GI) tract of osteoporotic Sprague-Dawley rat induced by ovariectomy were studied by Masson-Hamperl silver stain. The experimental animals were divided into two groups, one is non-ovariectomized group (Sham) and the other is ovariectomized group (OVX). Samples were collected from each part of GI tract (fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum) at 10th week after ovariectomy or sham operation. Argentaffin cells were detected throughout the entire GI tract with various frequencies regardless of ovariectomy except for the rectum of OVX in which no cells were detected. Most of these argentaffin cells in the mucosa of GI tract were generally spherical or spindle in shape (open type cell) while cells showing round in shape (close type cell) were rarely found in gland regions. Significant decrease of argentaffin cells was detected in OVX compared to that of Sham except for the fundus and jejunum. However, in the fundus and jejunum, argentaffin cells in OVX showed similar frequency compared to that of Sham. In conclusion, the endocrine cells are the anatomical units responsible for the production of gut hormones that regulate gut motility and digestion including absorption, and a change in their density would reflect the change in the capacity of producing these hormones and regulating gut motility and digestion. Ovariectomy induced severe quantitative changes of GI argentaffin endocrine cell density, and the abnormality in density of GI endocrine cells may contribute to the development of gastrointestinal symptoms in osteoporosis such as impairments of calcium and some lipids, frequently encountered in patients with postmenopausal osteoporosis.

• 대한예방한의학회지
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• 제18권2호
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• pp.133-145
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• 2014

Objective : In this study, the addition of dried pomegranate concentrate powder (PCP) was affected the anti-climacterium activity of red clover dry extracts (RC) in ovariectomized (OVX) rats. Materials and methods : After bilateral OVX surgery, RC 40 mg/kg, PCP 20 mg/kg and RC:PCP 2:1 mixture (g/g) 120, 60 and 30 mg/kg (of body weight) were orally administered, once a day for 84 days, and then the changes on the serum estradiol levels, abdominal fat pad and uterus weights were observed for estrogenic effects. In addition, liver weights, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were also evaluated for hepatoprotective effects, and serum total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride (TG) levels were monitored for hypolipidemic effects. Results : As a result of OVX, the estrogen-deficient climacterium symptoms, increments of abdominal fat pad weights, serum AST, ALT, TC, LDL and TG levels with decrease of uterus and liver weights, serum estradiol levels, were demonstrated. However, these estrogen-deficient climacterium symptoms induced by bilateral OVX in rats were significantly inhibited by continuous oral treatment of RC 40 mg/kg, PCP 20 mg/kg and RC:PCP 2:1 mixture (g/g) 120, 60 and 30 mg/kg, respectively. Conclusion : The results suggested that RC:PCP 2:1 mixtures synergistically increased the anti-climacterium effects of RC in OVX rats. It, therefore, is expected that RC:PCP 2:1 mixture will be promising as a new potent protective agents for relieving the climacterium symptoms.

• Advances in Traditional Medicine
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• 제1권1호
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• pp.97-106
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• 2000

The preventive effect of herbal formulation, ‘Dae-Bo-Won-Chun’(DBWC), on the progress of bone loss induced by ovariectomy (OVX) was studied in rats. From light microseopic analyses, a porous or erosive appearances were observed on the surface of trabecular bone of tibia in ovariectomized rats. Whereas those of the same bone in sham rats were composed of fine particles. The trabecular bone area and trabecular thickness in ovariectomized rats decreased by 50% from those in sham-operated rats, these decreases were completely inhibited by administration of DBWC at concentration of 10mg/kg per day for 7 weeks. The mechanical strength in femur neck was decreased by ovariectomy, and this was significantly suppressed by the administration of DBWC. Serum phosphorus, alkaline phosphatase, and thyroxine levels in ovariectomized rats were increased compared to those in sham-operated rats, and increases were completely inhibited by the administration of DBWC. These results strongly suggest that DBWC is effective in preventing the development of bone loss induced by ovariectomy in rats.

• International Journal of Industrial Entomology and Biomaterials
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• 제24권2호
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• pp.63-68
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• 2012

Osteoporosis is characterized by the reduced density of mineralized bone matrix. The loss of bone has been attributed to an imbalance between bone formation and bone resorption. The silkmoth is one of the famous traditional tonic medicines. Silkworm pupa was evaluated for its antiosteoporotic activity in an ovariectomized rat model of osteoporosis. The rats were ovariectomized at 6weeks of age and divided into 7 groups. All the groups were fed without calcium diet. The OVX rats were treated with water and silkworm powder for 6 weeks. In OVX rats, the body weight, feeding and water intake quantity did not show a significant change, but the silkworm pupa powder immediately before the eclosion of Yeonrokjam was significantly increased the bone mineral density in the femoral bone. The silkworm pupa powder increased the bone with increasing calcium in serum. These results also showed its protective action through promotion of bone formation. The silkworm pupa powder has a definite antiosteoporotic effect; similar to estrogen, it is especially effective for the prevention of bone fracture induced by estrogen deficiency. The silkworm pupa powder is a promising anti-osteoporotic agent that can prevent bone fractures in osteoporotic patients. The silkworm pupa powder does not show serious side effects because natural herbal medicine origin.

• Archives of Pharmacal Research
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• 제26권11호
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• pp.917-924
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• 2003

This research aims to test a new drug candidate based on a traditional medicinal herb, F1, an herbal extract obtained from Astragalus membranaceus and its main ingredient, 1-monolinolein that may have fewer side effects and less uterine hypertrophy. In vitro experiments, human osteoblast-like cell lines, MG-63 and Saos-2, were analyzed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and an alkaline phosphatase (ALP) assays. Mouse osteoclasts were induced through a calcium-deficient diet and inhibition effects were measured. In vivo experiments were done using ovariectomized (OVX) rats for 9 weeks. At necropsy, uterus weights were measured, trabecular bone area (TBA) of tibia and lumbar vertebra were measured bone histomorphology. In results, cell proliferation and ALP activity in Saos-2 by ether F1 or 1-monolinolein did not increased significantly compared to the control. The F1 inhibited osteoclast development ($IC_{25}=3.37{\times}10^{-5}$mg/mL) less than 17$\beta$-estradiol. The OVX rats administered F1 (2 mg/kg/day and 10 mg/kg/day) showed an increase in TBA of the tibia significantly (136.3${\pm}4.2% and 138.5{\pm}$10.3% of control). In conclusions, the herbal extract, F1 inhibited tibia and lumbar bone loss and did not cause uterine hypertrophy. However, 1-monolinolein, the main ingredient of the herbal extract, did not inhibit bone loss.

• 한국식품영양과학회지
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• 제35권1호
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• pp.48-54
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• 2006

우리나라는 노인인구의 증가에 따라 골다공증과 같은 골격질환자가 증가하고 있으며 국민 식생활 평가에서 칼슘섭취의 부족이 좀처럼 해결되지 못하고 있다. 보론이 식물성 식품에 풍부하다는 연구결과를 고려할 때 식물성 식품을 많이 섭취하는 우리나라에서 칼슘과 보론과의 관계를 규명하는 연구는 매우 필요하다고 생각한다. 따라서 본 연구에서 흰쥐를 대상으로 칼슘과 보론의 섭취수준을 달리하여 4주간 사육한 후 난소절제군과 비절제군으로 나눠 다시 8주간 사육하여 칼슘과 보론의 섭취수준이 칼슘평형에 미치는 영향을 살펴보았다. 사료섭 취 량과 체중증가량은 칼슘 섭취량이 높을수록, 난소절제군이 비절제군보다 높았다. 사료효율은 난소절제군이 비절제군보다 높았다. 혈청 중 칼슘 함량은 보론 보충에 따라 저칼슘군에서는 증가하였으나 적정과 고칼슘군에서는 감소하였다. 칼슘평형에서 칼슘 섭취량은 칼슘과 보론 섭취량이 높고 난소 적출을 한 경우 높은 것으로 나타났다. 대변 중 배설량은 난소 절제와 비절제군 모두 칼슘 섭취량이 증가할수록 높았으며, 소변 중 배설량은 칼슘 섭취량이 높을수록 증가한 반면, 보론 보충에 따라서는 감소하였다. 칼슘의 겉보기 흡수율은 칼슘 적정군과 난소절제군이 다른 군보다 높았으며, 칼슘 보유량은 칼슘 섭취량이 증가할수록 고칼슘군에서 난소절제군이 비절제군보다 높았다. 이상의 연구결과를 종합할 때 칼슘의 섭취량이 증가할수록 대변 중 칼슘 배설량이 증가하였지 만 칼슘 보유량은 증가하였고 칼슘의 겉보기 흡수율은 적정 칼슘군이 가장 높았다. 보론의 보충에 따라 칼슘의 겉보기 흡수율과 보유량은 유의한 변화가 없었지만 칼슘 섭취량은 증가하고 소변 중 칼슘 배설량은 감소하여 보론은 칼슘만큼 뚜렷한 영향은 아니지만, 체내의 칼슘이용을 촉진하고 배설을 감소시킴으로써 골격건강에 유용한 작용을 하는 것으로 나타났다.

• 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.

• 한국식품영양과학회지
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• 제30권4호
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• pp.657-661
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• 2001

이소플라본 보충이 골다공증의 예방 및 치료에 미치는 영향을 관찰하고자 Sprague-Dawley 암컷을 수술없이 일반식이를 제공한 군(CON), sham-operation 후 일반식이를 제공한 군(SH), 난소절제한 뒤 일반식이를 제공한 군(OVX), 난소절제 후 isoflavone을 공급한 군(OL, OM, OH)으로 나눈 뒤, 난소절제 4일 및 8주 후부터 8주간 이소플라본을 공급하여 혈액의 ALP, sy 중의 hydroxyproline의 변화, 골밀도, 골강도 및 골무게 등을 연구하였다. 골다공증의 예방에 대하여 isoflavone의 효과를 관찰한 결과, ALP는 난소를 절제한 OVX군에서는 CONrns과 SH군에 비해 유의적으로 높은 값을 보였다. 그러나, 난소절제 후 4일부터 8주간 isoflavone을 보충시킨 결과 ALP 활성과 urinary hydroxyproline 함량은 SH군과 비슷하게 낮아졌다. 특히 OM(0.8mg/kg diet)군의 경우 ALP활성과 urnary hydroxyproline 함량이 가장 낮아서 OVX군과 유의적인 차이를 보였다.(p<0.05). 난소적출 후 8주 후에 골밀도를 측정한 결과 난소절제군의 골밀도가 CONrns과 SH군에 비해 유의적으로 낮은 것으로 나타났다. Isoflavone을 보충한 결과 골밀도가 증가하였으나 유의적인 차이는 없어다. 골다공증의 치료효과에 대한 연구결과 alkaline phosphatase activity의 감소, 골밀도, 골강도 및 골무게가 증가하였으나 유의적인 차이는 나타나지 않았다. 이상의 결과는 난소절제 후에 일어나는 골격 대사의 이상은 isoflavone을 보충시킴으로써 어느 정도 정상화시킬 수 있음을 시사한다. 따라서 적절한 양의 isoflavone 보충은 폐경 후 여성의 골대사에 유익한 효과를 줄 것으로 풀이된다.