Effects of vitamin D on ovary in DHEA-treated PCOS rat model: A light and electron microscopic study

Aim: The aim of this study was to investigate the effects of vitamin D treatment on ovary in experimentally designed polycystic ovary syndrome of female rats using light and electron microscopic techniques. Methods: Twenty-four female pre-pubertal rats were divided into control, DHEA and DHEA+Vit.D groups. In DHEA group, the PCOS rat model was developed by 6mg/kg/day dehydroepiandrosterone administration as subcutaneously injections. In DHEA+Vit.D group, 6 mg/kg/day DHEA and 120ng/100g/week 1,25(OH)2D3 was performed simultaneously. Controls were injected with vehicle alone. At the end of the 28 days, blood samples were collected and the ovarian tissues were taken for histological examinations. Results: FSH, LH levels, LH/FSH ratio, and testosterone levels showed a significant increase in DHEA group when compared with the control group. Moreover, these measurements were lower in the treatment group than the DHEA group. In DHEA group, increased number of atretic follicles and cystic follicles were seen with light microscopic analysis. Cystic follicles with attenuated granulosa cell layers and thickened theca cell layers and lipid accumulation in interstitial cells were observed by electron microscope. It is observed that atretic and cystic follicles were decreased as a result of vitamin D treatment. Conclusion: Our results indicate the curative role of vitamin D treatment on the androgen excess in PCOS rat model which causes abnormalities in ovarian morphology and functions. Vitamin D has positive effects on the hormonal and structural changes observed in PCOS, but it has been concluded that long-term use may be more beneficial.     

戊酸雌二醇改善多囊卵巢综合征大鼠氯米芬诱导的子宫内膜容受性

目的探讨戊酸雌二醇(E2V)对多囊卵巢综合征(PCOS)大鼠氯米芬促排卵子宫内膜容受性的改善作用。方法将大鼠分为对照组(0.9%氯化钠溶液灌胃)、PCOS模型组(50 mg/kg氯米芬灌胃)、E2V低、中和高剂量干预组[(0.2、0.5、1.0)mg/kg E2V+50 mg/kg氯米芬灌胃]。用ELISA检测血清性激素水平;观察子宫内膜形态学变化;用RT-qPCR和Western blot检测子宫内膜中雌激素受体(ER)、孕激素受体(PR)、同源框基因(Hox)A10、空通气孔同源框(Emx)2、整合素(integrin)αvβ3 mRNA和蛋白表达情况。结果与对照组相比,PCOS模型组大鼠黄体生成激素/卵泡生成激素(LH/FSH)、睾酮(T)水平、Emx2 mRNA和蛋白相对表达量均明显升高(P<0.05),雌二醇(E2)水平、腺体面积、腺腔面积、子宫内膜厚度及腺/间质面积比、ER、PR、HoxA10、integrinαvβ3 mRNA和蛋白相对表达量均明显降低(P<0.05);与PCOS模型组相比,E2V低、中和高剂量干预组上述指标变化均相反(P<0.05)。结论 E2V可改善PCOS大鼠的氯米芬促排卵子宫内膜容受性,推测与上调ER、PR、HoxA10、integrinαvβ3 mRNA和蛋白表达,下调Emx2 mRNA和蛋白表达有关。     

c-Jun氨基末端激酶介导的细胞凋亡和自噬参与调控磷酸三钙磨损颗粒诱导的小鼠颅骨假体周围骨细胞死亡

目的 探讨c-Jun氨基末端激酶（JNK）介导的细胞凋亡和自噬是否参与调控磷酸三钙（TCP）磨损颗粒诱导假体周围骨细胞死亡。 方法 取雄性ICR小鼠36只,随机分为3组：正常对照组（control,n=12）、TCP磨损颗粒组（模型组,n=12）和SP6000125组（n=12）。采用TCP磨损颗粒30 mg置于颅骨顶后缝合皮肤构建小鼠颅骨溶解模型,SP6000125组小鼠于术后第2天颅顶注射JNK通路特异性抑制剂SP600125（1.0 mg/kg）,每3日1次。持续干预2周后处死小鼠取颅骨。Calcein-AM探针标记和HE染色观察各组假体周围骨细胞形态和活性变化;通过酶消化法获取假体周围骨细胞,应用流式细胞术检测假体周围骨细胞凋亡情况;Western blotting法检测假体周围骨细胞中Bcl-2、Bax、磷酸化JNK（p-JNK）、Beclin-1和微管相关蛋白1轻链3（LC-3）等蛋白的表达变化。 结果 与control组比较,TCP组假体周围骨细胞活性明显降低,空骨陷窝比例显著增加,骨细胞凋亡明显（P<0.05）,JNK通路被活化,p-JNK蛋白表达明显上调（P<0.05）;自噬相关蛋白Beclin-1和LC-3表达显著上调,且LC-3I向LC-3II转换明显增加（P<0.05）;与TCP组比较,SP600125组假体周围骨细胞凋亡显著减少、自噬被明显抑制（P<0.05）。 结论 JNK介导的细胞凋亡和自噬参与调控TCP磨损颗粒诱导的假体周围骨细胞死亡,促进假体周围骨溶解。     

Delayed healing and induction of secretory leukocyte protease inhibitor in polycystic ovary syndrome rat skin wounds

Secretory leukocyte protease inhibitor (SLPI) and estrogen promote wound healing through a decrease in the excessive inflammatory response, accelerating re-epithelialization and increasing the amount of collagen deposition. The excessive administration of estradiol valerate (EV) using hormonal therapy decreases the concentration of estrogen abruptly and induces the polycystic ovary syndrome (PCOS). In this study, the PCOS rat skin wound area was wider than that of the normal groups and the rate of keratinocyte migration in PCOS was lower than the normal group. The numbers of inflammatory cells and macrophages recruited in the PCOS group were larger than that of the normal group. More collagen was deposited in the healing area of the normal group than in the PCOS group. The level of SLPI expression was higher in the PCOS group than the normal group after wounding, with the exception of the epithelium. On the other hand, mRNA and protein expression levels of transforming growth factor-β1 (TGF-β1) were lower in the PCOS group than in the normal group. Matrix metalloproteinase-2 (MMP-2) and MMP-9 levels in the PCOS group were significantly lower than that of the normal group. Therefore, increased SLPI in PCOS skin wounds may help prevent an excessive inflammatory response and aberrant collagen deposition but not are sufficient to accelerate PCOS skin wound healing, suggesting that SLPI may act as a local rather than a systemic modulating molecule in PCOS rat skin wounds.     

Drospirenone increases central and peripheral beta-endorphin in ovariectomized female rats

OBJECTIVE: Drospirenone is the unique progestin derived from 17-spironolactone used for contraception and hormone therapy. Few data are available concerning the effects of drospirenone on the central nervous system and neuroendocrine milieu. The opioid beta-endorphin and the neurosteroid allopregnanolone are considered markers of neuroendocrine functions, and their synthesis and activity are regulated by gonadal steroids. The aim of the present study was to evaluate the effect of a 2-week oral treatment with drospirenone, estradiol valerate, and combined therapy of drospirenone + estradiol valerate on central and peripheral beta-endorphin and allopregnanolone levels in ovariectomized female rats. DESIGN: Seven groups of Wistar ovariectomized rats received oral drospirenone (0.1, 0.5, and 1.0 mg/kg per day), estradiol valerate (0.05 mg/kg per day), or drospirenone (0.1, 0.5, and 1.0 mg/kg per day) + estradiol valerate (0.05 mg/kg per day). One group of fertile and one group of ovariectomized rats were used as controls. beta-endorphin levels were measured in frontal and parietal lobes, hippocampus, hypothalamus, anterior and neurointermediate pituitary, and plasma, and allopregnanolone content was assessed in frontal and parietal lobes, hippocampus, hypothalamus, anterior pituitary, adrenal glands, and serum. RESULTS: Ovariectomy induced a significant decrease in beta-endorphin and allopregnanolone content in all brain areas analyzed and in circulating levels, whereas it increased allopregnanolone content in the adrenal gland. Estradiol valerate replacement increased beta-endorphin and allopregnanolone levels in all brain areas analyzed and in plasma/serum. Drospirenone treatment significantly increased beta-endorphin levels in all brain areas analyzed (with the only exception being the parietal lobe), whereas it produced no effect on allopregnanolone levels. The addition of drospirenone to estradiol valerate did not modify the effects of estradiol valerate on beta-endorphin or allopregnanolone levels. Drospirenone showed an additive and synergistic effect with estradiol in the neurointermediate lobe on beta-endorphin synthesis. CONCLUSIONS: Drospirenone significantly increases central and circulating beta-endorphin levels and does not seem to interfere with allopregnanolone production.     

Accelerated restoration of the leukocyte number and augmented resistance against Escherichia coli in cyclophosphamide-treated rats orally administered with a hot water extract of Chlorella vulgaris

The effects of oral administration of a hot water extract of Chlorella vulgaris (CVE) on the restoration of the leukocyte number and on the resistance against Escherichia coli infection were examined in cyclophosphamide (CY)-treated rats. Male Fischer rats (F344/DuCrj) were administered orally 1000 mg/kg of CVE for 14 days and injected intraperitoneally with a single dose of CY (50 mg/kg) (day 0) one day after the 14th CVE administration. CVE was further administered continuously after CY treatment until the rats were sacrificed for analysis. The number of bone marrow cells in the CY + CVE group was significantly higher on day 7 after CY treatment than that in the CY-treated group. The number of spleen cells in the CY + CVE group became significantly higher on day 11 than that in the CY-treated group. In the peripheral blood, the number of PMN recovered efficiently in the CY + CVE group in comparison with the CY-treated group on day 7. When E. coli was injected i.p. into normal, CY-treated, and CY + CVE-treated rats on day 6, the difference in number of bacteria among these three groups was most prominent before 6 h, that is, the number in the CY + CVE group was remarkably lower than those in the CY-treated group, and even in the control group, among all organs so far tested.     

Expression of SIRT1 in the ovaries of rats with polycystic ovary syndrome before and after therapeutic intervention with exenatide

Aim: To investigate the expression of silent information regulator 1 (SIRT1) in rats with polycystic ovary syndrome (PCOS) and its alteration after exenatide treatment. Methods: PCOS rat model was established by dehydroepiandrosterone induction. The animals were randomly divided into exenatide treatment group (EX group, n = 10), metformin treatment group (MF group, n = 10), PCOS group (PCOS group, n = 9) and normal control group (NC group, n = 10). Histological changes of the ovarian tissues were examined by HE staining. SIRT1 expression in the ovarian tissue was detected by RT-PCR and immunohistochemistry. Results: Rats in the PCOS group lost their estrous cycle. Histological observation of the ovary showed saccular dilatation of the follicle, decreased number of corpora lutea, fewer layers of granulosa cells aligned loosely, and thickened layer of theca cells. The changes in reproductive hormones and the development of insulin resistance suggested the successful establishment of the animal models. Immunohistochemistry and Q-PCR detected the mRNA and protein expressions of SIRT1 in the ovary tissues of rats in the normal control group. The SIRT1 expression was significantly lower in PCOS group than in control group (P < 0.05); after drug intervention, the SIRT1 expression significantly increased in EX and MF groups (compared with the PCOS group), whereas no significant difference was noted between the EX group and MF group. Conclusions: The SIRT1 expression in the ovary tissue decreases in PCOS rats (compare with the normal rats) but can be up-regulated after Ex or MF treatment. These drugs may affect the process and development of PCOS by regulating the SIRT1 expression. Exenatide may be therapeutic for PCOS by up-regulating the SITR1 expression.     

来曲唑诱导大鼠多囊卵巢综合征模型卵巢组织中CYP19基因的表达

目的:研究来曲唑诱导的多囊卵巢综合征(PCOS)模型大鼠卵巢组织中CYP19基因的表达,为该模型的应用提供一定的理论依据.方法:SD大鼠随机分为模型组和对照组,模型组应用来曲唑诱导大鼠PCOS模型.放射免疫法测定大鼠血清性激素水平;H-E染色观察卵巢组织学变化,免疫组织化学、Real time-PCR和免疫印迹法检测CYP19基因在卵巢组织中的表达.结果:模型组血清性激素水平睾酮、黄体生成素、卵泡刺激素浓度显著增高,雌二醇、孕酮浓度降低.模型组CYP19mRNA及蛋白表达均显著高于对照组.结论:来曲唑诱导的PCOS大鼠卵巢组织中CYP19基因表达水平增高.     

CCK-8上调LPS诱导的大鼠肺组织HO-1表达的信号转导机制

目的： 旨在研究八肽胆囊收缩素（CCK-8）上调脂多糖（LPS）诱导的大鼠肺组织中血红素氧合酶（HO）-1表达的信号转导机制。方法: 将42只雄性SD大鼠随机分为7组（每组6只）,即对照组、LPS组、LPS+SP600125（JNK特异性抑制剂）组、CCK-8+LPS组、CCK-8+LPS+SP600125组、CCK-8组、CCK-8+SP600125组。注药后6 h放血处死动物留取肺组织,应用RT-PCR、Western blotting和免疫荧光流式细胞术（FCM）等技术分别检测各组肺组织HO-1 mRNA和蛋白表达。结果: 与正常对照组相比,LPS组可见肺组织中出现明显的HO-1 mRNA表达的阳性信号,CCK-8可使LPS诱导的阳性表达信号进一步增强,CCK单独作用也可上调HO-1表达。信号密度扫描结果显示,LPS组、CCK-8+LPS组和CCK-8组HO-1 mRNA表达强度分别是正常对照组3.01（P<0.01）、5.88（P<0.01）和3.45倍（P<0.01）;JNK特异性抑制剂SP600125抑制了CCK-8和（或）LPS诱导的HO-1 mRNA表达;Western blotting、免疫荧光FCM检测结果显示,肺组织HO-1蛋白表达变化与其mRNA表达一致。结论: JNK/c-Jun通路在CCK-8上调LPS诱导肺组织HO-1表达过程中发挥重要作用。     

Serum adiponectin levels in women with polycystic ovary syndrome

BACKGROUND: Adiponectin is regarded as a possible link between adiposity and insulin resistance. The study aim was to measure serum adiponectin levels in women with polycystic ovary syndrome (PCOS) and to assess possible correlations between adiponectin and the hormonal or metabolic parameters of the syndrome. METHODS: Eighty-five selected women were classified as: Group I (n = 35) with PCOS + body mass index (BMI) >25 kg/m(2); group II (n = 35) with PCOS + BMI <25 kg/m(2); and group III (controls; n = 15) ovulating without hyperandrogenaemia and BMI <25 kg/m(2). Blood samples were collected between the days 3 and 6 of a spontaneous menstrual cycle, at 09:00, after an overnight fast. Serum levels of FSH, LH, prolactin, 17alpha-OH-progesterone, sex hormone-binding globulin (SHBG), androgens, insulin, adiponectin and glucose were measured. RESULTS: Adiponectin levels were significantly decreased in group I compared with groups II and III. No significant difference in adiponectin levels was found between groups II and III, despite significant differences in insulin levels and glucose:insulin ratio. Multiple regression analysis showed that Delta(4)-androstenedione levels and BMI values were the only significant determinants of serum adiponectin levels. CONCLUSIONS: Serum adiponectin levels are reduced in obese women with PCOS. Although adiponectin does not seem to be actively involved in the pathogenesis of PCOS, there seems to be an interaction between adiponectin and steroid synthesis or action.     

Effect of Lycopene and Rosmarinic Acid on Gentamicin Induced Renal Cortical Oxidative Stress,Apoptosis, and Autophagy in Adult Male Albino Rat

Gentamicin nephrotoxicity accounts for 10%–15% of all cases of acute renal failure. Several natural antioxidants were found to be effective against drug‐induced toxicity. The possible protective effects of lycopene (Lyc) and rosmarinic acid (RA) alone or combined on gentamicin (Gen) induced renal cortical oxidative stress, apoptosis, and autophagy were evaluated. Sixty‐three rats were randomly divided into seven groups named: control, group II received RA 50 mg/kg/day, group III received Lyc 4 mg/kg/day, group IV received Gen 100 mg/kg/day, group V (RA + Gen), group VI (Lyc + Gen), and group VII (RA + Lyc + Gen). At the end of the experiment, kidney functions were estimated then the kidneys were sampled for histopathological, immunohistochemistry, and biochemical studies. Administration of rosmarinic acid and lycopene decreased elevated serum creatinine, blood urea nitrogen, renal malondialdehyde and immunoexpression of the proapoptotic protein (Bax), autophagic marker protein (LC3/B), and inducible nitric oxide synthase (iNOS) induced by gentamicin. They increased reduced glutathione, glutathione peroxidase, superoxide dismutase, and immunoexpression of the antiapoptotic protein (Bcl2). They also improved the histopathological changes induced by gentamicin. The combination therapy of rosmarinic acid and lycopene shows better protective effects than the corresponding monotherapy. Anat Rec, 300:1137–1149, 2017. © 2016 Wiley Periodicals, Inc.     

Low-dose combination of flutamide,metformin and an oral contraceptive for non-obese,young women with polycystic ovary syndrome

BACKGROUND: The endocrine-metabolic status of non-obese, young women with polycystic ovary syndrome (PCOS) is normalized more effectively by combined treatment with flutamide and metformin than by either of these drugs in monotherapy. In this follow-up study, we assess whether the endocrine-metabolic benefits of combined flutamide-metformin treatment are maintained in the presence of a low-dose oral contraceptive (OC). METHODS: To a population of non-obese, young PCOS women already receiving flutamide-metformin (125 mg/day and 1275 mg/day), a low-dose OC (ethinyl estradiol 20 microg + gestodene 75 microg) was administered to reduce the risk of pregnancy. A total of 12 women elected to receive the OC and this subgroup (OC+) was matched to a subgroup continuing on flutamide-metformin alone (OC-), for a total study population of 24 women (mean age +/- SEM 18.7 +/- 0.3 years; body mass index, 21.8 +/- 0.5 kg/m(2)). Endocrine-metabolic indices were assessed before any treatment (0 months), on flutamide-metformin (12 months), and again after a further 6 months with or without additional OC (18 months). RESULTS: In OC- and OC+ women, the beneficial effects of flutamide-metformin on hyperandrogenaemia, hyperinsulinaemia and dyslipidaemia were maintained. In OC+ women, there was an additional increase in sex hormone-binding globulin (SHBG), and thus a further drop in the free androgen index. CONCLUSION: When a low-dose OC is administered with a low-dose flutamide-metformin combination in women with PCOS, the beneficial effects are maintained on hyperinsulinaemia-dyslipidaemia, which are key determinants of long-term complications. Hence, in daily practice, such a low-dose quatuor may become a therapeutic option of first choice for young women with PCOS.     

GLUT4在多囊卵巢综合征大鼠子宫内膜中的表达及意义

目的： 探讨葡萄糖转移因子4（GLUT4）在多囊卵巢综合征（PCOS）大鼠子宫内膜中的表达，评价其与子宫内膜胰岛素抵抗(IR)的关系。方法: 54只85日龄SD雌性大鼠，随机分为：① 对照组（20只）；② PCOS组（17只）；③ 二甲双胍治疗组（17只）。其中后两组先参照Poretsky等的方法复制PCOS大鼠模型，造模成功后，再分别喂服安慰剂或二甲双胍， 14 d后断头处死各组大鼠并取材。采用免疫组织化学染色Elivision^TM Plus两步法检测对照组、PCOS组及治疗组大鼠子宫内膜GLUT4蛋白的表达。结果: PCOS组大鼠子宫内膜腺上皮中GLUT4和INS-R蛋白表达明显低于对照组（P＜0.01，P＜0.05），INS蛋白表达水平明显高于对照组水平（P＜0.01）；治疗组GLUT4表达显著高于PCOS组（P＜0.01），但仍低于对照组（P＜0.01），INS表达较PCOS组显著降低（P＜0.05），但仍高于对照组（P＜0.05）；子宫内膜间质中无GLUT4的表达，INS和INS-R表达情况与腺上皮相似。结论: PCOS大鼠子宫内膜GLUT4表达减少和子宫内膜的IR有关。     

抗癫痫药妥泰对大鼠胚胎骨骼发育影响的研究

目的 研究妥泰(TPM)高、低剂量单药及与丙戊酸钠(VPA)合用对大鼠胚胎骨骼发育的影响。方法 采用妊娠雌性SD大鼠随机分为5组。实验组3组，于妊娠6～15d分别经口灌胃给予TPM40mg/kg，TPM80mg/kg和TPM40mg／kg VPA300mg／kg。阴性对照组同期经口灌胃给以等量的蒸馏水。阳性对照组于妊娠第11d一次性腹腔注射环磷酰胺(CP)10mg／kg于妊娠第20d处死孕鼠，将胎仔茜素红和阿利新蓝骨骼双染后，检查全身骨骼发育程度。结果 TPM高剂量组及与丙戊酸钠联合用组仔鼠骨骼发育迟缓，与阴性对照组相比有明显的差异。但TPM低剂量组无显著差异。结论 TPM在低剂量时对大鼠胚胎骨骼发育影响较小，而高剂量及与丙戊酸钠联合用药时影响较大。     

Flutamide-metformin plus an oral contraceptive (OC) for young women with polycystic ovary syndrome: switch from third- to fourth-generation OC reduces body adiposity

BACKGROUND: Low-dose flutamide-metformin has been developed as a background therapy for non-obese adolescents and young women with hyperinsulinaemic hyperandrogenism, a variant of polycystic ovary syndrome (PCOS). We verified whether the lipolytic efficacy of flutamide-metformin in women with PCOS is enhanced by giving an oral contraceptive (OC) co-therapy that contains drospirenone, instead of gestodene, as progestin. METHODS: An open-labelled study was carried out in which non-obese women with PCOS (n = 29; age approximately 20 years), who had been on a combination of flutamide (62.5 mg/day), metformin (850 mg/day) and ethinylestradiol-gestodene for 8-15 months, were randomized for replacement of the gestodene OC by a drospirenone OC. Assessments of endocrine-metabolic state and body composition (by dual-energy X-ray absorptiometry) were performed at randomization and after 6 months. RESULTS: The switch to drospirenone OC was accompanied by a reduction of total and abdominal fat (mean -0.8 and -0.5 kg) and by an increment of lean body mass (+0.6 kg; all P < 0.01), so that body adiposity was strikingly reduced without changing body weight. CONCLUSION: In non-obese women with PCOS, low-dose flutamide-metformin reduces total and abdominal fat excess more effectively if contraceptive co-therapy contains drospirenone, instead of gestodene, as progestin.     

Benefits and risks of different hormonal replacement therapies in post-menopausal women

A total of 113 women who presented with climacteric symptoms participated in the study. They were randomly allocated to seven groups of 10–27 subjects, who received for 6 mth the following therapies, respectively: (1) conjugated oestrogens (CE) 0.625 mg/day for 21 days + norethisterone (NET) 5 mg/day from day 12 to day 21; (2) CE + cyproterone acetate (CPA) 12.5 mg/day from day 1 to day 10; (3) oestradiol valerate (EV) 2 mg/day for 21 days + NET; (4) EV + CPA; (5) oestriol (E₃) 2–4 mg/day; (6) tibolone (ORG OD14) 2.5 mg/day; and (7) placebo, one tablet/day.

Hot flushes decreased significantly over the treatment period in all seven groups. However, E₃ was less effective at the dose used than CE, EV or ORG OD 14. At the end of the 6 month treatment period histological examination revealed no changes in endometrial morphology in any of the patients treated. Indeed, the addition of a progestogen even induced regression of endometrial hyperplasia in 8 cases.

No significant variation in the plasma levels of tryglycerides, total cholesterol, high-density lipoprotein (HDL) or low-density lipoprotein (LDL) was observed after the second and sixth months of treatment with E₃ or ORG OD 14. After 6 months, treatment with CE/EV + CPA produced a significant increase in HDL, while treatment with CE/EV + NET brought about a reduction in total cholesterol and HDL and an increase in LDL.     

Body weight reduction and metformin: Roles in polycystic ovary syndrome

Background and objectives: Polycystic ovary syndrome (PCOS) is a common problem in women at fertile age. A prospective study was conducted to clarify the pathophysiological responses during an application of insulin sensitizer, metformin and weight reduction therapy at the Gynecology Center in Ohud hospital, in AL-Madinah AL-Munawarah, Kingdom of Saudi Arabia. Methodology: Twenty healthy women served as controls and 180 PCOS women divided into three groups participated in the study. First group was treated with Clomid citrate 100 mg/day from the 2nd day of menses to the 6th day plus gonadotrophin from day three to the 13th. Group II was treated as group I plus 850 mg metformin twice a day and group III was treated as group I plus weight reduction. Clinical symptoms, menstrual pattern, hirsutism, blood glucose, body mass index, waist-to-hip ratio, insulin, hormonal, and lipid profiles were assessed pre- and post treatment. Insulin resistance was calculated. Results: PCOS women had significantly higher values than the healthy women in most of the measurements. Metformin and weight reduction therapy resulted in a significant decrease in the fasting insulin, glucose/insulin ratio and HOMA-IR. Metformin and weight reduction therapy resulted in a significant decrease in the lipid parameters, testosterone, LH/FSH ratio, SHBG, and prolactin levels. HOMA-IR was significantly higher in women with PCOS. HOMA-IR was positively correlated with testosterone, estradiol, TG, total cholesterol and LDL-cholesterol parameters, and negatively correlated with HDL-cholesterol and FSH levels. Conclusion: Metformin therapy and weight reduction had favorable influences on the basic metabolic and hormonal profiles in women with PCOS and that metformin and lifestyle modification (weight reduction via diet restriction or exercise) resulted in a significantly greater weight loss than hormonal therapy alone. Metformin and weight reduction therapy decreased also hyperandrogenism and insulin resistance.     

来曲唑诱导多囊卵巢综合征大鼠卵巢组织中GATA-4的表达

目的 探讨GATA-4在多囊卵巢综合征( PCOS) 发病机制中的作用,并为来曲唑诱导的PCOS模型的应用提供一定的理论依据. 方法 40只雌性SD大鼠随机分为模型组和对照组,模型组来曲唑1mg/(kg·d)溶于10g/L羧甲基纤维素(CMC)中,连续灌服21d;对照组给予同体积的溶剂(CMC)灌服.放射免疫法测定大鼠血清性激素水平;HE染色观察卵巢组织学变化;免疫组织化学、实时定量PCR和免疫印迹法检测GATA-4在卵巢组织中的表达. 结果 模型组血清睾酮(T)、促黄体生成素(LH)、促卵泡刺激素(FSH)浓度显著增高,雌二醇(E2)、孕酮(P)浓度降低.与对照组比较,模型组可见囊状扩张卵泡明显增多,卵巢白膜增厚,黄体数量明显减少.模型组卵巢窦前卵泡和窦状卵泡颗粒细胞GATA-4表达显著增强,卵巢组织中GATA-4mRNA及蛋白表达水平均显著高于对照组(P<0.05). 结论 卵泡颗粒细胞GATA-4表达异常增高与多囊卵巢综合征的发生密切相关.来曲唑诱导的PCOS动物模型是研究PCOS病理机制的一种理想的动物模型.     

Comparison of the effects of acarbose and metformin use on ovulation rates in clomiphene citrate-resistant polycystic ovary syndrome

BACKGROUND: The aim of this study was to evaluate the effects of metformin and acarbose on insulin resistance, hormone profiles and ovulation rates in patients with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). METHODS: Thirty clomiphene citrate-resistant patients were selected randomly and divided into two groups. Group I was treated with 100 mg/day clomiphene citrate and 300 mg/day acarbose 100 mg/day orally, for 3 months. Group II was treated with clomiphene citrate 100 mg/day and metformin 1700 mg/day orally, for 3 months. Serum fasting insulin and glucose, FSH, LH, estradiol, progesterone, prolactin and total testosterone levels plus body mass index (BMI) were measured before and after treatment. Follicle growth was followed by transvaginal ultrasonography. RESULTS: LH:FSH ratio and total testosterone concentrations decreased (P<0.05) and ovulation rates increased in both groups. Reduction in weight and BMI was only significant in the acarbose group. CONCLUSIONS: Both treatment modalities were effective in the treatment of insulin resistance and improving ovulation rates. Increase in the number of eumenorrhoeic and normoinsulinaemic cases and decrease in the number of insulin-resistant cases were significant in both groups (P<0.05). Ovulation rate was greater in the metformin group in the second month of therapy (P<0.05). Acarbose was found to be a safe and effective agent that could be used in cases with clomiphene-resistant PCOS.