PCOS患者卵巢胰岛素抵抗的发生机理探讨

目的:探讨胰岛素抵抗/高胰岛素血症在PCOS生殖功能障碍中的作用。方法:收集行IVF-ET治疗的11例PCOS患者(PCOS组)和15例排卵正常的输卵管性不孕患者(对照组)促排卵后卵巢黄素化颗粒细胞,行体外培养,分别用不同浓度胰岛素处理细胞48h,采用RT-PCR和Westernblot检测黄素化颗粒细胞胰岛素受体底物(IRS)-1和IRS-2mRNA及蛋白的表达。采用放射免疫法检测血清性激素及空腹血清胰岛素(FIN)水平;采用葡萄糖氧化酶法测定空腹血糖(FPG)水平;计算胰岛素抵抗指数(HOMA-IR)。结果:①PCOS患者血清LH、LH/FSH、T、FIN及HOMA-IR均明显高于对照组(P<0.05);②0mU/ml胰岛素时,PCOS组黄素化颗粒细胞IRS-1mRNA及蛋白的表达水平明显高于对照组(P<0.05),而IRS-2mRNA及蛋白的表达水平较对照组明显降低(P<0.05);③10mU/ml胰岛素对二组患者黄素化颗粒细胞IRS-1和IRS-2mRNA及蛋白的表达均无影响(P>0.05);④100mU/ml或1000mU/ml胰岛素作用后,二组患者IRS-1mRNA及蛋白的表达水平均明显增高(P<0.05),而IRS-2mRNA及蛋白的表达水平均明显降低(P<0.05)。结论:PCOS患者胰岛素抵抗/高胰岛素血症通过提高卵巢颗粒细胞IRS-1的表达,降低IRS-2的表达参与患者卵巢生殖功能障碍的发生。     

血清抵抗素、C-反应蛋白及IL-6与PCOS的相关性研究

目的:探讨血清脂肪细胞因子抵抗素(resistin)、C-反应蛋白(CRP)、白细胞介素6(IL-6)水平与PCOS发生的相关性。方法:收集PCOS患者45例,再根据体质量指数(BMI)分为肥胖亚组(≥25kg/m2,22例)和非肥胖亚组(<25kg/m2,23例)。正常对照组45例,同样按BMI分为肥胖亚组(14例)和非肥胖亚组(31例)。空腹采集血清,采用酶联免疫分析法测定抵抗素、免疫比浊法测定CRP、放射免疫法测定IL-6,全自动生化分析仪测定血糖、血脂、化学发光法测定内分泌水平和血清胰岛素水平,同时测量身高、体质量、腰围、臀围,计算BMI和腰臀比值(WHR)。结果:与对照组非肥胖者相比,PCOS组肥胖、非肥胖者及对照组肥胖者抵抗素水平均显著增高(P<0.05);PCOS组和对照组肥胖者的CRP水平均高于对照组非肥胖者(P<0.05);PCOS组肥胖和非肥胖者的IL-6水平高于对照组非肥胖者(P<0.05)。抵抗素和CRP均与BMI、WHR、HOMA-IR呈显著正相关(P<0.05);IL-6与BMI、WHR有显著相关性,与HOMA-IR无相关性。结论:脂肪细胞因子抵抗素、CRP及IL-6参与PCOS患者肥胖和胰岛素抵抗的发生发展。     

多囊卵巢综合征患者脂联素、C反应蛋白水平的变化及其意义

目的:探讨脂联素(APN)、C反应蛋白(CRP)的变化对多囊卵巢综合征(PCOS)发病的意义。方法:按体重指数(BMI≥25kg/m2或<25kg/m2)分别将PCOS患者52例、对照组47例分为PCOS肥胖组(25例)、非肥胖组(27例)和对照肥胖组(23例)、对照非肥胖组(24例)4组。用ELISA法测定4组的APN水平、散射比浊法测CRP水平,葡萄糖氧化酶法测定空腹血糖(FPG)、化学发光法测空腹胰岛素(FIN)水平,并计算胰岛素抵抗指数(HOMA-IR)。结果:①PCOS组APN水平低于对照组(P<0.05),且同组肥胖者低于非肥胖者。②PCOS组CRP水平高于对照组(P<0.05),且肥胖者高于非肥胖者。③APN水平与BMI、HOMA-IR水平呈明显负相关(P<0.05)。结论:PCOS组APN水平降低,CRP水平升高,且以肥胖者明显。APN水平降低、CRP水平升高与PCOS患者胰岛素抵抗密切相关。     

肥胖与非肥胖多囊卵巢综合征患者血清肿瘤坏死因子-α(TNF-α)水平的比较

目的:比较肥胖与非肥胖多囊卵巢综合征(PCOS)患者血清肿瘤坏死因子-α(TNF-α)水平的差异。方法:55例PCOS患者,根据体质量指数(BMI)分为肥胖组(BMI>25,n=31)和非肥胖组(BMI≤25,n=24);同期选择50例非PCOS育龄妇女,分为肥胖对照组(BMI>25,n=25)和非肥胖对照组(BMI≤25,n=25)。应用酶联免疫吸附法(ELISA)测定血清TNF-α的含量,分析TNF-α与胰岛素抵抗指数(HOMA-IR)的相关性。结果:PCOS肥胖组与PCOS非肥胖组的TNF-α水平分别显著高于其相应的对照组(P<0.01),PCOS非肥胖组的TNF-α水平也显著高于肥胖对照组(P<0.05)。PCOS肥胖组与PCOS非肥胖组之间的TNF-α水平无显著差异(P>0.05)。PCOS组TNF-α与HOMA-IR呈显著正相关(P<0.05)。结论:肥胖与非肥胖PCOS患者的血清TNF-α水平均升高,可能存在肥胖以外升高TNF-α的途径;TNF-α与PCOS的IR发生有密切联系。     

血浆内脂素与多囊卵巢综合征的相关性

目的 探讨血浆内脂素与多囊卵巢综合征(PCOS)及肥胖的关系.方法 选择2008年1～6月在徐州医学院附属医院妇产科确诊为PCOS的患者70例,将PCOS组患者根据体重指数(BMI)分为肥胖者(BMI≥25)34例和非肥胖者(BMI<25)36例;选择同期就诊的非PCOS不孕患者和健康志愿者60例为对照组(肥胖者30例,非肥胖者30例).采用酶联免疫吸附法(ELISA)检测两组空腹血浆内脂素浓度,同时测定身高、体重、腰围、臀围、空腹血糖(FBS)、空腹胰岛素(FINS),计算BMI、腰臀比(WHR)、胰岛素抵抗指数(HOMA-IR).结果 PCOS组肥胖、非肥胖患者血浆内脂素[分别为(66.31±14.93)μg/L和(45.52±18.67)μg/L]明显高于对照组肥胖、非肥胖者[分别为(41.03±17.93)μg/L和(26.94±13.38)μg/L],差异有统计学意义(P<0.05);PCOS组肥胖患者血浆内脂素浓度高于非肥胖患者,差异有统计学意义(P<0.05).相关分析显示PCOS患者血浆内脂素浓度与BMI呈正相关(r=0.402,P<0.05),而与WHR、FBS、FINS、HOMA-IR无相关性.结论 PCOS患者存在高内脂素血症,内脂素水平与BMI呈正相关,提示内脂素可能参与PCOS与肥胖的发病机制.     

血清脂联素水平测定在多囊卵巢综合征中的意义

目的:探讨脂联素水平在多囊卵巢综合征(PCOS)中的意义。方法:选择我院PCOS患者48例作为研究对象,同期选择非PCOS患者40例作为对照,分为肥胖组与非肥胖组,胰岛素抵抗组与非胰岛素抵抗组。测定血清脂联素水平及内分泌代谢指标。结果:①PCOS组血清脂联素水平低于对照组(P<0.05);非肥胖PCOS组低于非肥胖对照组(P<0.05);胰岛素抵抗组低于非胰岛素抵抗组(P<0.05)。②血清脂联素水平与体重指数(BMI)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、腰臀比(WHR)、甘油三酯(TG)呈负相关(P<0.01,P<0.05),与葡萄糖胰岛素比值(GIR)、胰岛素敏感指数(ISI)呈正相关(P<0.01)。控制BMI影响后血清脂联素水平仍与HOMA-IR、TG呈负相关(P<0.05),与GIR、ISI呈正相关(P<0.01)。结论:①PCOS患者存在低脂联素血症,脂联素水平与胰岛素抵抗程度呈负相关。②脂联素可以作为PCOS发生糖尿病远期并发症的预测指标。     

血清促生长激素释放激素受体配体与多囊卵巢综合征的相关性分析

目的:探讨血清促生长激素释放激素受体配体(Ghrelin)水平在多囊卵巢综合征(PCOS)中的意义.方法:选择我院PCOS患者48例作为研究对象(PCOS组),同期选择非PCOS患者40例作为对照(对照组),根据体重指数(IBM)将PCOS组、对照组患者分别分为肥胖与非肥胖,根据稳态模型胰岛素抵抗指数(HOMA-IR)将PCOS组及全部患者分为胰岛素抵抗(IR)与非IR.测定血清Ghrelin水平及内分泌代谢指标.结果:血清Ghrelin水平PCOS组低于对照组(P<0.05);肥胖组低于非肥胖组(P<0.05);非肥胖组低于非肥胖对照组(P<0.05);IR组低于非IR组(P<0.05).血清Ghrelin水平与BMI、空腹胰岛素(FINS)、HOMA-IR呈负相关(P<0.01,P<0.05,P<0.05),与胰岛素敏感指数(ISI)呈正相关(P<0.05).结论:PCOS患者存在血清低Ghrelin水平,Ghrelin水平与BMI、IR程度呈负相关.Ghrelin可能与PCOS的肥胖发生有相关性.血清Ghrelin检测可能作为预测PCOS患者IR的一个指标.     

多囊卵巢综合征患者血清miR-3188、miR-3585表达与肥胖、糖脂代谢和胰岛素抵抗的相关性

目的:分析多囊卵巢综合征(PCOS)患者血清微小RNA-3188(miR-3188)及微小RNA-3585(miR-3585)的表达与肥胖、糖脂代谢和胰岛素抵抗的相关性,探讨miR-3188及miR-3585诊断PCOS的价值。方法:选取2018年1月至2021年10月两家医院收治的152例PCOS患者(PCOS组)和60例健康女性(对照组)。PCOS患者根据胰岛素抵抗指数(HOMA-IR)分为胰岛素抵抗组(n=99,HOMA-IR≥2.69)和非胰岛素抵抗组(n=53,HOMA-IR<2.69);根据体质量指数(BMI)分为肥胖组(n=49,BMI≥28 kg/m~2)和非肥胖组(n=103,BMI<28 kg/m~2)。采用实时荧光定量PCR法检测各组血清miR-3188及miR-3585表达水平。应用受试者工作特征曲线(ROC)分析miR-3188及miR-3585对PCOS的诊断价值。Pearson相关分析miR-3188、miR-3585表达水平与肥胖指标、糖脂代谢指标和HOMA-IR的相关性。结果:PCOS组血清miR-3188(2.65±0.94 vs 1.04±0.26)及miR-3585(2.18±0.72 vs 0.85±0.17)表达水平均明显高于对照组(P<0.001)。肥胖组血清miR-3188(3.40±1.18 vs 1.95±0.63)及miR-3585(2.81±1.02 vs 1.59±0.41)表达水平均明显高于非肥胖组(P<0.001)。胰岛素抵抗组血清miR-3188(3.51±1.24 vs 1.83±0.57)及miR-3585(2.90±1.07 vs 1.52±0.38)表达水平均明显高于非胰岛素抵抗组(P<0.001)。ROC曲线显示,miR-3188及miR-3585两项联合诊断PCOS的曲线下面积最大(0.895,95%CI 0.834～0.953),其敏感度为93.8%,特异度为78.5%。相关分析显示,PCOS患者血清miR-3188及miR-3585表达水平与BMI、腰臀比、甘油三酯、低密度脂蛋白、空腹胰岛素水平及HOMA-IR均呈正相关(r>0,P<0.05)。结论:PCOS患者血清miR-3188及miR-3585表达水平明显上调,且与肥胖、糖脂代谢和HOMA-IR有关,miR-3188及miR-3585联合检测对PCOS诊断具有较好的参考价值。     

瘦素调节人卵巢黄素化颗粒细胞功能的体外研究

目的　探讨瘦素、促卵泡激素 (FSH)和胰岛素样生长因子Ⅰ (IGF Ⅰ )对人卵巢黄素化颗粒细胞雌二醇 (E2 )、孕酮 (P)生成的影响及可能的作用机制。方法　培养人黄素化颗粒细胞 ,分别以瘦素 (3 0ng/ml)、FSH (1 0ng/ml)、IGF Ⅰ (30 0ng/ml)以及相同终浓度的瘦素 +FSH、瘦素 +IGF Ⅰ、FSH +IGF Ⅰ、瘦素 +FSH +IGF Ⅰ对其刺激 2 4h ,对照组不加任何药物。对药物作用后的黄素化颗粒细胞行形态学观察、细胞计数 ;用放射免疫法检测培养液中E2 和P水平 ;同时用逆转录聚合酶链反应法对黄素化颗粒细胞行瘦素受体mRNA检测。结果　瘦素、FSH和IGF Ⅰ对黄素化颗粒细胞生长无影响。瘦素对黄素化颗粒细胞E2 生成量无影响 ,对FSH刺激E2 的生成也无影响 ,E2 水平作用前分别为 (0 10 3± 0 0 36 )pmol/10 0 0细胞、(0 32 3± 0 0 4 2 )pmol/10 0 0细胞 ,作用后分别为 (0 12 0± 0 0 0 8)pmol/10 0 0细胞、(0 343± 0 0 34)pmol/10 0 0细胞 ;而对IGF Ⅰ、FSH +IGF Ⅰ刺激黄素化颗粒细胞生成E2 有显著的抑制作用 ,E2 水平作用前后分别为 (0 318± 0 0 37)pmol/10 0 0细胞与 (0 4 93± 0 0 36 )pmol/10 0 0细胞、(0 193± 0 0 2 5 )pmol/10 0 0细胞与 (0 2 5 1± 0 0 33)pmol/10 0 0细胞 (P <0 0 5 ,<0     

脂肪组织中胰岛素受体底物1蛋白的表达及酪氨酸磷酸化在多囊卵巢综合征发病中的作用

目的探讨多囊卵巢综合征(PCOS)患者脂肪组织胰岛素受体底物1(IRS1)的蛋白表达及酪氨酸磷酸化在PCOS发病中的作用。方法采用免疫沉淀法、Western印迹法和增强化学发光蛋白免疫印迹法及图像分析半定量检测24例PCOS患者[PCOS组,根据体重指数分为肥胖(体重指数≥24kg/m2)和非肥胖(体重指数<24kg/m2)者各12例]及同期因卵巢囊肿或输卵管阻塞行开腹手术的非PCOS患者24例(对照组,根据体重指数分为肥胖和非肥胖者各12例)的脂肪组织中IRS1的蛋白表达及酪氨酸磷酸化程度。结果PCOS组肥胖者IRS1的蛋白表达为(82±15)%,PCOS组非肥胖者为(79±18)%;对照组肥胖者为(75±19)%,对照组非肥胖者为(70±19)%,各组间比较,差异均无统计学意义(P>005)。脂肪组织中IRS1的酪氨酸磷酸化程度在PCOS组肥胖者为(52±23)%,对照组非肥胖者为(88±12)%,两者比较,差异有统计学意义(P<001);对照组肥胖者为(45±22)%,PCOS组非肥胖者为(70±25)%,与对照组非肥胖者比较,明显降低,差异均有统计学意义(P<001,P<005);PCOS组肥胖者和对照组肥胖者间以及PCOS组肥胖者和PCOS组非肥胖者间比较,差异均无统计学意义(P>005)。结论PCOS组脂肪组织IRS1的蛋白表达及酪氨酸磷酸化程度明显减弱,可能参与胰岛素受体后信号传导抑制,并与PCOS胰岛素抵抗的发生有     

Local effect of bisphenol A on the estradiol synthesis of ovarian granulosa cells from PCOS

Close relationship between polycystic ovary syndrome (PCOS) and bisphenol A (BPA) has drawn much attention in recent years, while the underlying mechanisms are poorly understood. In our study, we aim to detect BPA concentration in the follicular fluid and investigate its effect on estradiol synthesis in human granulosa cells from PCOS and non-PCOS patients. Follicular fluid and granulosa cells were collected from women who underwent controlled ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection. BPA concentration in the follicular fluid from PCOS patients (440.50?±?63.70?pg/ml) was significantly higher than that from non-PCOS patients (338.00?±?57.88?pg/ml). Expression of aromatase and estradiol synthesis in cultured granulosa cells was examined after treatment with BPA from 0.01 to 1?μM for 24?h. Expression of aromatase and estradiol synthesis was downregulated by BPA in a dose-dependent manner in PCOS, but no effect was observed in granulosa cells from non-PCOS patients. These findings provide evidence that increased BPA concentration in the follicular fluid of PCOS patients may play an important role in its pathogenesis by attenuating the expression of aromatase in granulosa cells.     

Effects of leptin on basal and FSH stimulated steroidogenesis in human granulosa luteal cells

BACKGROUND: Body weight influences fertility and studies in mice have indicated that leptin is one of the mediators of this effect. Leptin is believed to centrally stimulate the hypothalamic-pituitary axis resulting in increased gonadotropin release. Moreover, leptin is present in follicular fluid and the receptor is expressed in the human ovary. The aim of this study was to evaluate the direct effect of leptin on cultured human granulosa cell steroidogenesis. METHODS: Granulosa cells were obtained in connection with IVF procedures, and then cultured in a serum-free medium containing androstenedione (1 microM) for a total of 4 days. After 2 days of culture the medium was changed and the hormones under study were added. We tested the effect of leptin (1, 20, 100 ng/ml) on basal, FSH (10-100 ng/ml), and FSH (10-100 ng/ml)+IGF-I (30 ng/ml) stimulated steroidogenesis. RESULTS: Leptin (20 ng/ml and 100 ng/ml) significantly reduced basal and FSH-stimulated estradiol secretion (p<0.05). Basal and FSH (10 and 30 ng/ml) stimulated progesterone production was significantly inhibited by leptin 20 ng/ml, whereas leptin 100 ng/ml significantly reduced basal but not FSH stimulated progesterone production. Finally, steroidogenesis stimulated by IGF-I alone and in combination with FSH was not influenced by leptin. CONCLUSION: These results suggest that leptin acts directly to inhibit basal and FSH stimulated estradiol and progesterone production in cultured human granulosa cells. This raises the possibility that high circulating leptin levels as seen in obese women may compromise fertility through peripheral mechanisms.     

Serum leptin levels in patients with polycystic ovary syndrome

OBJECTIVE: To determine whether polycystic ovary syndrome (PCOS) is related to leptin dysregulation. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology in a university hospital. PATIENT(S): Fifty patients with PCOS (33 nonobese and 17 obese) and 32 control women (19 nonobese and 13 obese) were included in the study. INTERVENTION(S): Serum leptin levels were measured in patients with PCOS and the controls. Correlations between leptin levels and serum hormone levels (FSH, LH, free testosterone, androstenedione, DHEA-S and fasting insulin) were studied. MAIN OUTCOME MEASURE(S): Serum leptin levels and correlations between leptin levels and the hormonal parameters. RESULT(S): Mean serum leptin levels were not significantly higher in patients with PCOS compared to the control group. Leptin levels were found to be significantly higher in the obese subgroups both in patients with PCOS and in the control women. Leptin levels were found to be higher in obese patients with PCOS compared to obese controls; however, when the levels were evaluated again with covariance analysis excluding body mass index, there was no statistically significant difference. Leptin levels had a positive correlation with body mass index, both in patients with PCOS and the controls. CONCLUSION(S): Leptin levels were not higher in patients with PCOS compared to the control group; the leptin level was correlated with the amount of fat tissue not only in patients with PCOS but also in healthy women.     

Clinical significance of serum concentration of anti-Müllerian hormone in obese women with polycystic ovary syndrome

In the human ovary, expression of anti-Müllerian hormone (AMH) is detected primarily in granulosa cells of preantral and small antral follicles. The aim of this study was to compare serum AMH measurements in obese women with polycystic ovary syndrome (PCOS) with those in obese normo-ovulatory women and to evaluate the role of AMH as a predictor of ovulation induction by clomiphene citrate compared to FSH. Sixty-eight obese women with PCOS were compared to 17 normoovulatory obese women. All women had a body mass index greater than 30 kg/m(2). Women with PCOS received clomiphene citrate (150 mg/day) for 5 days starting from day 3 of cycle and were subdivided into responsive and non-responsive groups. There was a significant difference in AMH concentration between women with PCOS and the control group (P < 0.05) and also between women with PCOS who responded to clomiphene citrate and those who did not (P < 0.01). A value of 1.2 ng/ml AMH could be used to predict response to clomiphene citrate in obese women with PCOS (sensitivity 71%, specificity 65.7%). AMH production increases in women with PCOS compared to controls. AMH measurement could also be useful in the prediction of ovarian response to clomiphene citrate.     

Relationship between serum anti-Mullerian hormone and intrafollicular AMH levels in PCOS women

Polycystic ovary syndrome is a complex disease characterized by various endocrine disorders that are the potential cause of anovulation and hyperandrogenism. Anti-Müllerian hormone expression is suspected to be overexpressed in PCOS granulosa cells. AMH acts as a regulator of folliculogenesis: it is produced by the granulosa cells of follicles from the stage of the primary follicle to the initial formation of the antrum. Serum and intrafollicular AMH levels are elevated in patients with PCOS due to increased number of small follicles and an increased secretion within each of these small follicles. This excess of AMH is strongly suspected to play a role in the characteristic follicular arrest of PCOS, through a negative action on aromatase expression and on FSH action. Value above 5?ng/ml or 35?pmol/l might be considered as a diagnostic criterion for PCOS. The aim of our study is to demonstrate the presence of higher AMH serum levels and higher AMH intrafollicular fluid level of PCOS patients, undergone to IVF cycles, compared to normovulatory patients. The results clearly indicate that blood and intrafollicular AMH levels are significantly higher in PCOS women comparing to the normovulatory population. Serum AMH level appears to be a good predictive marker for the risk ovarian hyperstimulation syndrome: thus, its evaluation should be recommended before starting a controlled ovarian stimulation for IVF.     

瘦素对人卵巢黄素化颗粒细胞雌、孕激素分泌的体外实验研究

目的探讨瘦素在体外对人卵巢颗粒细胞雌激素和孕激素生成的影响。方法将来自体外受精-胚胎移植（IVF-ET）的卵巢黄素化颗粒细胞纯化后，在不同浓度瘦素(0、10、30、100、300ng/ml)和人绝经期促性腺激素（hMG，0、0.1、0.2、0.5、1、2、5、10IU/ml）单独或联合作用下进行体外培养，收集培养液，采用放射免疫方法测定颗粒细胞产生雌二醇及孕酮的量。结果不同浓度的瘦素对雌二醇、孕酮的生成无影响；hMG为5IU/ml时，雌二醇水平平均为2.36×10-11mol/L，加入不同浓度瘦素（10、30、100、300ng/ml），雌二醇的生成均受到明显的抑制，随瘦素浓度增加，雌二醇水平逐渐降低（P<0.05），孕酮水平无明显变化；hMG浓度小于0.5IU/ml时，瘦素对雌二醇生成无影响；hMG浓度大于0.5IU/ml、瘦素为100ng/ml时，雌二醇水平低于不加瘦素的对照（P<0.05）。结论瘦素参与卵巢颗粒细胞激素生成的调节，在卵泡发育和黄体形成中有一定的作用。     

Vascular endothelial growth factor and leptin: regulation in human cumulus cells and in follicles

BACKGROUND: The factors that determine oocyte competency are poorly understood. It is believed that angiogenic factors are crucial. Modulation of these factors is therefore a central consideration. The adjacent association of cumulus cells to oocytes gives these cells a particular importance in relation to oocyte behavior. We report the effects of gonadotropins on the secretion of VEGF and leptin from cumulus cells; and the concentrations of the proteins in follicular fluid and their relationship to fertilization of oocytes in vitro. METHODS: The subjects were women undergoing intracytoplasmic sperm injection (ICSI). Oocytes and follicular fluid were collected. Leptin and vascular endothelial growth factor (VEGF) concentrations in incubation supernatants and follicular fluid and leptin in cell lysates were measured. Fertilization of corresponding oocytes were noted. In the present study, cells from individual follicles were incubated, as well as pooled cells from a woman. RESULTS: For the first time we demonstrated that VEGF release by human cumulus cells was modulated by gonadotropins in a dose-related, time-dependent manner, but no leptin was detected in either the supernatants after cumulus cell incubations or in cell lysates. Mean leptin levels were similar whether from follicles associated with eggs that were fertilized (14.4 +/- 1.1 ng/ml, mean +/- SEM) or not (12.4 +/- 1.1 ng/ml). Mean VEGF levels were also similar (11.1 +/- 1.2 ng/ml; 12.8 +/- 1.3 ng/ml). A greater proportion of VEGF in follicles was derived from follicular activities, compared with transfer from other physiological compartments, than leptin. CONCLUSIONS: Whereas it is possible that VEGF is part of the gonadotropin-mediated network that regulates development of the oocyte, leptin may not be produced in significant quantities by cumulus cells or be related to oocyte competency.     

Leptin regulation of aromatase activity in adipose stromal cells from regularly cycling women.

OBJECTIVES AND DESIGN: Leptin, a product of adipocytes, is a cytokine with multiple effects on the reproductive axis. Leptin causes the activation of STAT proteins within target cells. The aromatase gene promoter in adipose stromal cells contains a functional STAT binding region, leading to the hypothesis that leptin may regulate aromatase activity in fat tissue. To test this hypothesis, adipose stromal cells were isolated from subcutaneous abdominal fat or breast fat then placed into tissue culture. MATERIALS AND METHODS: The cells were treated for three days with increasing concentrations of recombinant human leptin. Aromatase activity in the stromal cells was measured by the release of 3H2O from radiolabeled androstenedione precursor. RESULTS: Basal aromatase activity varied markedly between, but there were no differences between abdominal fat and breast fat. Leptin concentrations in the physiological range of normal weight or thin women (10 ng/ml) had no effect on aromatase activity. In 2 of 8 abdominal fat cultures and 1 of 2 breast fat cultures, a high obese concentration of leptin (100 ng/ml) stimulated a significant increase in aromatase activity. In the remaining subjects there was no effect of leptin, even at high concentrations. CONCLUSIONS: These data demonstrate that in approximately 30 percent of our subject population leptin was able to stimulate aromatase activity in adipose stromal cells at high concentrations. The elevated levels of aromatase activity may contribute to increase circulating estrogen levels in certain obese women and suggest that elevated leptin concentrations in obese women may cause locally elevated estrogen concentrations in the breast and thereby promote tumor formation.