The Tissue-selective Effect Of Daidzein On Bone, Uterus And Lacteal Gland Of The Ovariectomized Rats And The Receptor Mechanism Mediated By ERs And PPARγ

BackgroundEstrogen can effectively reduce the bone loss and incidence of fracture in post menopausal women.However,it may lead to an increase of breast cancer,uterine endometrial carcinoma and other adverse events.Phytoestrogen has potential benefits and becomes a hot of research.Daidzein is one of the most important phytoestrogen and show potential application prospects.It is revealed that phytoestrogens can protect bone mass to some extent,while some researches show the opposite result. These conflicting results might be due to the biphasic dose-dependent effects of phytoestrogen;however the related reports are few.It is still unknown the effects of phytoestrogens on lacteal gland and uterus.Recently,some researches have revealed that estrogen receptors and peroxisome proliferator-activated receptor gamma may mediate the dose-dependently bone-protective effect and tissue-selective effect of phytoestrogen,but whether it works in vivo is open to doubtPartâ… The Dose-dependent Effect of Daidzein on Osteoporosis in the Ovariectomized(OVX) Rats and its Effects on the Expression of mRNA and Protein of Bone Tissue's ERs and PPARγObjectiveTo investigate the effect of daidzein on the biochemical indexes of bone metabolism, bone mineral density,biomechanical testing,histomorphometry and the expression of ERα,ERβand PPARγmRNA and protein of bone tissue in the ovariectomized(OVX) rats,and discuss the dose-dependent effect and the molecular mechanisms of daidzein on osteoporosis in the ovariectomized rats.Materials and methodsSixty four-month-old Sprague-Dawley(SD) female rats were allotted to one of six groups.Four weeks after reproducing the osteoporosis model of ovariectomized SD rats,Sham group and control OVX were administrated with distilled water,whereas the other groups received valerate estriol(800μg/kg·d) and different doses of daidzein (10,50,200 mg/kg·d) by gavage respectively for three months.These parameterswere measured after the sacrifice of the rats.Using a dual energy x-ray absorptiometer,bone mineral density were measured in the lumbar spine L_1-5 and left femur.The expressions ofmRNA of ERa,ERβand PPARγin L₆ and right femur were measured by realtime-RT-PCR,while proteins were measured by immunohistochemistry.Results1,The BMD,biomechanical testing and histomorphometry of lumbar spine and left femur decreased in OVX group while these indexes increased in L-Dai group significantly.Except biomechanical testing of left femur,rats in M-Dai group showed all indexes higher than OVX group significantly,while only these indexes of lumbar spine of rats in H-Dai group higher significantly.2,The BMD and histomorphometry of lumbar spine and biomechanical testing of left femur in M-Dai group,and the BMD and histomorphometry of lumbar spine and BMD and biomechanical testing of left femur in H-Dai group,were all lower than L-Dai group significantly.3,The expressions of ERαmRNA and protein of lumbar spine and left femur in three Dai groups and OVX group showed no significant difference.4,The expressions of ERβmRNA and protein of lumbar spine and left femur in L-Dai and M-Dai groups were significantly higher than OVX group,while the protein expression of ERβof left femur in M-Dai group was lower than L-Dai group significantly.Only the expressions of ERβmRNA and protein of lumbar spine in H-Dai group were higher than OVX group significantly,and these of left femur between two groups showed no significant difference.5,The expressions of PPARγmRNA of bone in rats in three Dai groups decreased significantly compared with OVX group.H-Dai group was higher than other two Dai groups,but no significant difference between them.Conclusions1,Daidzein shows estrogen-like effect on bone,resulted into dose-dependent effect on prevention and treatment of osteoporosis in ovariectomized rats,while the low-dose of daidzein is more effective. 2,Both ERs expressed in lumbar spine and femur,however ERβwas more than ERa, which implied that the bone-protective effect of daidzein through ERβmainly.3,When daidzein in level of low dose,the level of expression of ERβin bone was higher.And the expression of ERβshowed lower trend and PPARγshowed higher trend with the dose of daidzein increasing.Which implied that there is a cross talk between ERβand PPARγ,and it is related with the dose-dependent effect of daidzein on osteoporosis in the ovariectomized rats.Partâ…¡The Tissue-selective Effect of Daidzein on Uterine Endometrial Tissue of the Ovariectomized RatsObjectiveTo investigate the effect of daidzein on the histomorphometry and the expression of mRNA and protein of ERa,ERβand PPARγin the ovariectomized(OVX) rats' uterine endometrial tissue,and discuss the tissue-selective effect and the molecular mechanisms of daidzein on uterine endometrial tissue of the ovariectomized rats.Materials and methodsUsing uterine endometrial tissues of rats in Partâ… ,we detected their histomorphometry, and the expressions of mRNA of ERa,ERβand PPARγrealtime-RT-PCR,while protein were by immunohistochemistry.Results1,The uterus weight of rats in three Dai groups increased,but no significant difference between them and OVX group.2,Uterine endometrial thickness and area of transverse section of rats in L-Dai and M-Dai groups showed no significant difference with OVX group,while the uterine endometrial thickness of rats in H-Dai group higher than OVX and L-Dai groups significantly.3,The expression of ERa mRNA and protein of uterine endometrial tissue were higher than OVX and L-Dai groups significantly.4,The expression of ERβmRNA of uterine endometrial tissue only could be detected in Sham and E₂ group,while the protein expression could not be detected in all groups.5,The level of PPARγof uterine endometrial tissue in three Dai groups decreased significantly,and there no significant difference between them,while the protein expression could not be detected in all groups.Conclusions1,L-Dai and M-Dai did not show estrogen-like effect on uterine endometrial tissue of OVX rats,however H-Dai may play weak estrogen-like effect through ERa.2,The uterine endometrial tissue mainly expresses ERα.3,The role of PPARγin uterine endometrial tissue of rats needs further researchs.Partâ…¢The Tissue-selective Effect of Daidzein on Lacteal Gland of the Ovariectomized RatsObjectiveTo investigate the effect of daidzein on the histomorphometry and the expression of mRNA and protein of ERa,ERβand PPARγin the ovariectomized(OVX) rats' breast, and discuss the tissue-selective effect and the molecular mechanisms of daidzein on lacteal gland of the ovariectomized rats.Materials and methodsUsing breast tissues of rats in Partâ… ,we detected their histomorphometry,and the expressions of mRNA of ERα,ERβand PPARγrealtime-RT-PCR,while protein were by immunohistochemistry.Results1,Rats in OVX group showed atrophic breast,without obvious acinar structure,and the same in three Dai groups.2,The expression of ERαmRNA of lacteal gland in three Dai groups were no significant difference with OVX group,but significantly lower than E₂ groups.3,The expression of ERβof breast was only detected in Sham and E₂ groups.4,The level of PPARγin three Dai groups decreased significantly,and there no significant difference between them.5,The expression of ERs and PPARγprotein were not detected in all groups.Conclusions1,Daidzein had no estrogen-like stimulation on breast of OVX rats,which may be related with ERa.2,The breast tissue mainly expresses ERα.3,The role of PPARγin lacteal gland of rats needs further researchs.Summary1,Daidzein shows tissue-selective effect on bone,uterus and lacteal gland of the OVX Rats.2,Daidzein shows estrogen-like effect on bone,resulted into dose-dependent effect on prevention and treatment of osteoporosis in ovafiectomized rats,while may be related with the cross talk between ERβand PPARγ.3,L-Dai and M-Dai did not show estrogen-like effect on uterine endometrial tissue, however H-Dai may play weak estrogen-like effect through ERα.4,Daidzein had no estrogen-like stimulation on breast.Chinese Library Classification:R71...