폐경 쥐 모델에서 두류 섭취에 따른 자궁의 비타민 D 수용체의 발현
Expression of Vitamin D Receptor by Pulse Consumption in the Uterus of Menopausal Mouse Model
2
조회
0
다운로드
3
인용
0
참고문헌
키워드
초록
연구목적: 식물성 에스트로겐이 포함된 두류 섭취는 폐경 증상 완화에 효과가 있다. 하지만 이런 효과가 어떻게 일어나는지는 명확하지 않다. 본 연구는 폐경 쥐 모델에서 폐경 후 변화에 두류가 미치는 영향을 살펴보았다. 연구재료 및 방법: Female Sprague-Dawley rats 16마리를 이용하였다. 3마리는 Sham operation을 시행하여 대조군으로사용하였고, 13마리는 양쪽 난소절제술을 시행하였다. Sham군에게는 AIN-93M diet (n = 3)를 공급하였고, 난소 절제한 rat을 세군으로 나누어 두류가 포함된 실험 식이를 공급하였다. 각 군마다 다른 실험 식이를 공급하고, 10주간 사육하였다. 마지막 주에 sacrifice하여 자궁을 적출하고 무게를 측정하였다. 적출한 자궁에서 비타민 D 수용체 (vitamin D receptor, VDR), 에스트로겐 수용체 (estrogen receptor, ER) β, ezrin의 발현을 면역조직화학염색을 통해 확인해 보았다. 결과: VDR은 폐경상태와 관계없이 자궁내에서 뚜렷하게 발현하였다. 오히려 난소를 절제한 군에서 VDR이 더 뚜렷하게 발현하고 있었다. ER β의 발현은 차이가 없었다. 하지만 녹두가 포함된 식이를 제공한 군에서 ezrin의 발현이 증가해 있었다 (P = 0.044). 결론: 이번 연구는 향후 두류 섭취로 인한 폐경 증상 완화 치료의 가능성을 분자생물학적인 관점에서 살펴보았다는데의의가 있다. 하지만 VDR, ER β 그리고 ezrin의 폐경 후 자궁에서의 역할에 대한 자세한 기전을 위해서는 더 많은 연구가 필요할 것으로 보인다.
Abstract
Objectives: Phytoestrogen-containing pulse supplements have beneficial effects on postmenopausal symptoms, but how such effects are achieved is unclear. This study investigates the effects of pulse consumption on the menopausal changes in ovariectomized rats. Methods: Female Sprague-Dawley rats were either sham operated (Sham; n = 3) or surgically ovariectomized (n = 13). The Sham group was fed the regular AIN-93M diet. Ovariectomized group was divided into 3 sub-groups and fed AIN-93M containing soybean (n = 5), mung bean (n = 3), or cowpea (n = 5) for 10 weeks. At the end of the experiment, all rats were sacrificed, and the uterus was harvested, rinsed, and weighed. Expressions of vitamin D receptor (VDR), estrogen receptor (ER) β, and ezrin in uterus were evaluated by immunohistochemistry. Results: VDR was highly expressed in the uterus of rat, irrespective of ovariectomized state. VDR was more definitely expressed in the uterus of ovariectomized groups than the sham-operated group. There were no significant differences in expression of ER β. However the expression of ezrin was highly expressed in the cowpea group compared to sham group (P = 0.044). Conclusion: This study suggested that legumes diet may concern menopausal changes via VDR and ezrin. The result may partly explain the beneficial effects of VDR on menopausal symptoms. Further study is necessary to study the detailed mechanisms of VDR and ezrin on the menopausal changes in the uterus.
참고문헌 (39)
- Anderson JW, "Cardiovascular and renal benefits of dry bean and soybean intake", Am J Clin Nutr, 70, pp.464S~474S (1999)
- Messina MJ, "Legumes and soybeans: overview of their nutritional profiles and health effects", Am J Clin Nutr, 70, pp.439S~450S (1999)
- Chen YM, "Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a doubleblind, randomized, controlled trial", J Clin Endocrinol Metab, 88, pp.4740~4747 (2003)
- Chiechi LM, "Efficacy of a soy rich diet in preventing postmenopausal osteoporosis: the Menfis randomized trial", Maturitas, 42, pp.295~300 (2002)
- Harkness L, "Soy and bone. Where do we stand", Orthop Nurs, 23, pp.12~17 (2004)
- Holick MF, "High prevalence of vitamin D inadequacy and implications for health", Mayo Clin Proc, 81, pp.353~373 (2006)
- Lips P, "Vitamin D physiology", Prog Biophys Mol Biol, 92, pp.4~8 (2006)
- Mosselman S, "ER beta: identification and characterization of a novel human estrogen receptor", FEBS Lett, 392, pp.49~53 (1996)
- Enmark E, "Human estrogen receptor beta-gene structure, chromosomal localization, and expression pattern", J Clin Endocrinol Metab, 82, pp.4258~4265 (1997)
- Tremblay GB, "Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor beta", Mol Endocrinol, 11, pp.353~365 (1997)
- Heldring N, "Estrogen receptors: how do they signal and what are their targets", Physiol Rev, 87, pp.905~931 (2007)
- Hess RA, "Estrogen in the adult male reproductive tract: a review", Reprod Biol Endocrinol, 1, pp.52~ (2003)
- McDonnell DP, "Capitalizing on the complexities of estrogen receptor pharmacology in the quest for the perfect SERM", Ann N Y Acad Sci, 949, pp.16~35 (2001)
- Kuiper GG, "The novel estrogen receptorbeta subtype: potential role in the cell- and promoterspecific actions of estrogens and anti-estrogens", FEBS Lett, 410, pp.87~90 (1997)
- Hiscox S, "Ezrin regulates cell-cell and cellmatrix adhesion, a possible role with E-cadherin", betacatenin, 1999, pp.112 Pt 18, 3081~3090
- Curto M, "Ezrin...a metastatic detERMinant", Cancer Cell, 5, pp.113~114 (2004)
- Athanasopoulou A, "Decreased ezrin and paxillin expression in human urothelial bladder tumors correlate with tumor progression", Urol Oncol (2011)
- Khanna C, "The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis", Nat Med, 10, pp.182~186 (2004)
- Hunter KW, "Ezrin, a key component in tumor metastasis", Trends Mol Med, 10, pp.201~204 (2004)
- Song J, "Estradiol-induced ezrin overexpression in ovarian cancer: a new signaling domain for estrogen", Cancer Lett, 220, pp.57~65 (2005)
- Smith PM, "Tissuespecific regulation by estrogen of ezrin and ezrin", radixin, Endocrine, pp.2003, 22[DOI]
- Baeza I, "Ovariectomy, a model of menopause in rodents, causes a premature aging of the nervous and immune systems", J Neuroimmunol, 219, pp.90~99 (2010)
- Zarnani AH, "Vitamin D3 receptor is expressed in the endometrium of cycling mice throughout the estrous cycle", Fertil Steril, 93, pp.2738~2743 (2010)
- Adlercreutz H, "Dietary phyto-oestrogens and the menopause in Japan", Lancet, 339, pp.1233~ (1992)
- Marini H, "Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial", Ann Intern Med, 146, pp.839~847 (2007)
- Roach VJ, "Phytoestrogens: dietary intake and excretion in postmenopausal Chinese women", Climacteric, 1, pp.290~295 (1998)
- Pan Y, "A comparison of oral micronized estradiol with soy phytoestrogen effects on tail skin temperatures of ovariectomized rats", Menopause, 8, pp.171~174 (2001)
- Lu LJ, "Phytoestrogens and healthy aging: gaps in knowledge. A workshop report", Menopause, 8, pp.157~170 (2001)
- Song AR, "A study on management of menopause of climacteric women", J Korean Soc Menopause, 3, pp.140~160 (1997)
- Knight DC, "Effects on menopausal symptoms and acceptability of isoflavonecontaining soy powder dietary supplementation", Climacteric, 4, pp.13~18 (2001)
- Lee SK, "Study on the impact of isoflavone in hormonal profiles during the menstrual cycle and in the postmenopausal parameters in Korean women", 박사, pp.2001
- Adams MR, "The atheroprotective effect of dietary soy isoflavones in apolipoprotein E-", - mice requires the presence of estrogen receptor-alpha, 2002, pp.22, 1859~1864
- Lichtenstein AH, "Approaches to reducing cardiovascular disease risk: food or pills", Curr Opin Lipidol, 12, pp.1~3 (2001)
- Alekel DL, "Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women", Am J Clin Nutr, 72, pp.844~852 (2000)
- Francis RM, "A comparison of the effects of alfacalcidol treatment and vitamin D2 supplementation on calcium absorption in elderly women with vertebral fractures", Osteoporos Int, 6, pp.284~290 (1996)
- Yildirim B, "The effects of postmenopausal vitamin D treatment on vaginal atrophy", Maturitas, 49, pp.334~337 (2004)
- Somjen D, "A non-calcemic vitamin D analog modulates both nuclear and putative membranal estrogen receptors in cultured human vascular smooth muscle cells", J Steroid Biochem Mol Biol, 89-90, pp.397~399 (2004)
- Nashold FE, "Estrogen controls vitamin D3-mediated resistance to experimental autoimmune encephalomyelitis by controlling vitamin D3 metabolism and receptor expression", J Immunol, 183, pp.3672~3681 (2009)
- Cavallini A, "Estrogen receptor (ER) and ER-related receptor expression in normal and atrophic human vagina", Maturitas, 59, pp.219~225 (2008)