Effect Of Oral And Transdermal Estrogen Replacement Therapy On T Lymphocytes Function Of Surgical Menopausal Women

BackgroundRecent studies have suggested that estrogen played an important role in immunemodulation and immune-related disorders, perhaps with estrogen receptors (ERs)involved. A rapid decline in female sex hormone production after menopause may thusaffect the immune response. People have payed more and mor attention to the effect ofestrogen replacement treatment (ERT) on immune function of menopausal womensince ERT was widely used. However, there are few researches about the effect of ERTon estrogen receptor (ER) subtypes expression and on immune balance of menopausalwomen.Partâ… The effect of different concentration of estradiol on estrogenreceptor expression and Th1/Th2 balance in splenocytes ofovariectomized miceObjectiveTo investigate the effect of different concentration of estradiol on ER subtypesexpression and T-helper 1/ T-helper 2 (Th1/Th2) balance in splenocytes ofovariectomized mice.MethodsThe female BALB/C mice (10-weeks old) splenocytes were divided into sevengroups: young group, sham-ovariectomized group, ovariectomized group and fourovariectomized plus estradiol groups (estradiol concentration: 10^-11mol/L,10^-10mol/L,10^-9 mol/L,10^-8 mol/L). The ERαand ERβmRNA expression wasdetermined by RT-PCR, specific cytokine(interferon-γ, interleukin-2 and interleukin-4)were evaluated by ELISA, which implied Th1/Th2 balance.Results 1,The ERα,ERβmRNA expression in ovariectomized group were significantly lowerthan that in young group and sham-ovariectomized group (P＜0.05 and P＜0.01).Compared with ovariectomized group, ERα,ERβmRNA expression inovariectomized plus estradiol (10^-10 mol/L) group increased (P＜0.05; P＜0.01),ERα,ERβexpression in ovariectomized plus estradiol(10^-8 mol/L) trended todecrease.2,IFN-γand IL-2 production in ovariectomized group were extremely higher thanthat in young group and sham- ovariectomized group (P＜0.01), however, IL-4level in ovariectomized group was lower than that in young group and sham-ovariectomized group (P＜0.05). IFN-γand IL-2 level in ovariectomized plusestradiol(10^-10 mol/L) group were significantly lower than that in ovariectomizedgroup (P＜0.01), but IL-4 production was higher than that in ovariectomized group(P＜0.05). IFN-γlevel in ovariectomized plus estradiol(10^-8 mol/L) group wassignificantly higher than that in ovariectomized group (P＜0.01), and IL-2 leveltrended to increase, while IL-4 trended to decrease.Conclusions1,Different concentration of estradiol effected differentially on ERα,ERβgeneexpression in splenocytes of ovariectomized mice. According to our results, wesupported that ERs expression was up-regulated at physiological doses of estrogenand down-regulated with the concertration of estrogen higher than physiologicaldoses.2,In mice ovariectomized, the Th1/Th2 balance was destroyed, which suggested Th1polarization. Physiological doses estrogen could partially decreased Th1 typecytokine and restored the Th1/Th2 balance.3,Estrogen effected the Th1/Th2 balance of splenocytes of mice by combining withERαand ERβ. Partâ…¡Effect of oral and transdermal estrogen replacement therapyon T lymphocytes function of surgical menopausal womenObjectiveTo investigate the effect of oral and transdermal estrogen replacement therapy(ERT) on expression of different estrogen receptors (ER) subtypes and T lymphocytesfunction of surgical menopausal women.Materials and methodsHealthy women who have underwent total hysterectomy and bilateral salpingo-oopherectomy within 0.5 to 1.5 years were distributed into two groups: the oral ERTgroup (17-β-estradiol, ling per day for 3month) and the transdermal ERT group,(17-β-estradiol, 50μg per day once a week for 3 month), and each group with 12 womenwho were not menopausal until the operation. We evaluated menopausal complaintsand life quanlities by "Improved Kuppeerman index" and "menopause-specific qualityof life questionnaire", scaled the serum estradiol (E₂) and FSH with fully automicroparticle chemiluminescence immune assay (ACCESS), examined T lymphocytesubsets of peripheral blood with flow cytometry (FCM) and the specific cytokine(IFN-γ,IL-2 and IL-4) secretion of T lymphocytes with ELISA, at the same time, wealso detected the ERαand ERβmRNA expression of peripheral blood T lymphocytesby real time RT-PCR, the ERαand ERβprotein expression with western-blot andimmunofluorescence. After 3 months ERT, all contents were detected again.Results1,The menopausal complaints and life quanlities have been improves afterERT(P＜0.01), no significant difference between oral ERT group and transdermalERT group.2,Level of serum E₂ of both groups after ERT was higher than the level before ERT(P＜0.01), but level of FSH after ERT was lower (P＜0.01), no significant differencebetween two groups.3,After ERT, the percentage of peripheral blood CD3⁺ lymphocytes and the ratio ofCD4⁺/CD8⁺ of both groups were significantly higher than the level before ERT(P＜0.01), no significant difference between two groups.4,Level of IL-2 and IFN-γafter ERT became lower, and no difference between the two groups; level of IL-4 was significantly higher after ERT in oral group andtransdermal group(P＜0.01 and P＜0.05), which might improve Th1/Th2 balance.5,The level of mRNA and protein of ERαof T lymphocyte significantly increasedafter ERT in both groups (P＜0.01), while the ERβexpression made no obviousdifference before and after ERT.Conclusions1,After oral or transdermal ERT, the menopausal complaints and life quanlities ofsurgical menopausal women were improved, and serum E₂ level was increased,while FSH level decreased.2,After ERT, the percentage of peripheral blood CD3⁺ lymphocytes as well as theratio of CD4⁺/CD8⁺ of both groups increased significantly.3,After ERT, the level oflL-2 and IFN-y secretion of T lymphocytes of both groupsdecreased, that of IL-4 of oral ERT group increased, which might improve Th1/Th2balance.4,Both oral and transdermal ERT increased ER expression, which was related to theincrease of serum E2.5,Both oral and transdermal ERT improved T lymphocytes function of surgicalmenopausal women, estrogen acts mainly through ER of T lymphocyte.6,When used for short time in early menopause, low-dose ERT can relieve effectlythe peri-menopausal symptom and improve the immune function.