激活素A和卵泡休止素与先兆子痫的相关性研究

目的　探讨先兆子痫患者血清中激活素A和卵泡休止素水平及其mRNA在胎盘组织中的表达 ,及其与先兆子痫发病的关系。方法　 2 0例足月妊娠先兆子痫孕妇作为先兆子痫组 ,2 0例足月妊娠血压正常孕妇作为对照组。应用酶联免疫吸附试验 (ELISA)检测两组孕妇血清中激活素A和卵泡休止素水平。应用半定量逆转录 聚合酶链反应 (RT PCR)技术检测两组孕妇分娩后胎盘组织中激活素AmRNA和卵泡休止素mRNA的相对表达强度。将两组孕妇的胎盘组织激活素AmRNA的表达强度与血清激活素A水平进行直线相关分析。结果　 (1)先兆子痫组孕妇血清中激活素A水平为 (33 7± 6 6 ) μg/L ,明显高于对照组的 (9 9± 2 1) μg/L(P <0 0 1)。先兆子痫组孕妇血清中卵泡休止素水平为 (5 1± 0 6 ) μg/L ,与对照组的 (4 7± 0 3) μg/L比较 ,差异无显著性 (P >0 0 5 )。 (2 )先兆子痫组胎盘组织中激活素AmRNA为 1 11± 0 2 1,明显高于对照组的 0 6 1± 0 17(P <0 0 1)。先兆子痫组胎盘组织中卵泡休止素mRNA为 0 5 7± 0 31,与对照组的 0 5 4± 0 2 7比较 ,差异无显著性 (P >0 0 5 )。(3)在先兆子痫组和对照组孕妇中 ,血清中激活素A水平与胎盘组织激活素AmRNA相对表达强度呈正相关 [相关系数 (r) =0 89,P <0 0 1]。结论     

Effect of hypoxia on placental activin A,inhibin A and follistatin synthesis

Placental activin A and inhibin A output is increased in pre-eclampsia, a condition characterized by placental hypoxaemia, whereas follistatin secretion is unaltered. We investigated whether hypoxia was the basis for elevated placental activin A and inhibin A output. First trimester and term placental explants were grown in 5-6% dissolved O(2) (n=10/trimester) and 200 microM cobalt chloride (CoCl(2),n =6/trimester) to simulate environmental and cellular hypoxia respectively, for up to 72 h. Activin A, inhibin A and follistatin production were compared with control cultures grown in standard media at 20% O(2). In first trimester and term placenta, activin A output declined significantly under 5-6% O(2) (P=0.006 and 0.001 after 48 h respectively). Inhibin A declined significantly under 5-6% O(2), mainly in first trimester placenta (P=0.03, 24h). CoCl(2) significantly elevated activin A production in term placenta (P=0.003, 48 h), whereas inhibin A output was unaffected. Neither low O(2) or CoCl(2) altered follistatin output from first trimester or term placenta. These findings suggest that there may be novel O(2) sensing mechanism/s that down regulate activin A and inhibin A in the placenta and that low O(2) is not the mechanism behind increased placental inhibin A or activin A output in pre-eclampsia.     

激活素A和卵泡休止素对人滋养层细胞增殖和激素分泌的调节作用

目的: 探讨激活素A和卵泡休止素对人早孕绒毛滋养层细胞的增殖和人绒毛膜促性腺激素及孕酮分泌的调节作用。方法: 早孕绒毛用胰蛋白酶与胶原酶联合消化后,再用小牛血清白蛋白密度梯度离心,分离纯化后所得的滋养层细胞进行体外原代培养。将不同浓度激活素A加入细胞培养液中作用48 h,观察其对滋养细胞生长和人绒毛膜促性腺激素及孕酮分泌的影响。向滋养层细胞培养液中加入激活素A和不同浓度的卵泡休止素,培养24 h,观察相互作用。结果: 激活素A和卵泡休止素都不影响滋养层细胞的增殖。激活素A以剂量依赖的方式促进滋养层细胞绒毛膜促性腺激素的分泌和孕酮的分泌,滋养细胞分别经30 ng/mL,100 ng/mL激活素A处理后,培液中绒毛膜促性腺激素和孕酮水平达到高峰(P均<0.01)。激活素A对滋养层细胞激素分泌的影响,可以被其特异结合蛋白卵泡休止素以剂量依赖方式阻断。结论: 激活素A和卵泡休止素以自分泌方式调节滋养层细胞绒毛膜促性腺激素和孕酮分泌,但并不影响细胞增殖,激活素A与卵泡休止素在人早期妊娠中起重要的生理作用。     

In-vivo concentrations of inhibins, activin A and follistatin in human early pregnancy

The aims of this study were to investigate the relationship between inhibins, activin A and follistatin in first trimester fetal fluids, maternal serum, placenta and decidua, and to investigate if these hormones are present in the circulation of the early second trimester human fetus. Amniotic and coelomic fluid, maternal serum, placental villi and decidual tissue were obtained from normal pregnancies at 8-12 weeks. Fetal blood by cardiocentesis and maternal blood were collected at 14-16 weeks gestation. Placental extracts had higher concentrations of inhibins, activin A and follistatin compared with decidual extracts. In the second trimester, inhibins and follistatin were detectable in fetal blood at 14-16 weeks gestation. Maternal serum concentrations of inhibin A (P < 0.001) and follistatin (P < 0.05) were significantly higher than fetal serum whereas inhibin B (P < 0.01) and pro-alpha C concentrations (P < 0.001) were higher in fetal serum. Inhibin B concentrations were also higher in male fetal serum samples that had higher concentrations of testosterone. The presence of all molecular forms of inhibins, activin A and follistatin in the first trimester fetal fluids, placental and decidual extracts in the first trimester confirms other reports. In the second trimester, high concentrations of inhibin B with testosterone in the fetal circulation indicate that these hormones may interact in the development of the male fetal gonads.     

The physiology and pathophysiology of inhibin,activin and follistatin in female reproduction

In the last 2 years, major advances have been made in the understanding of inhibin physiology. Discovery of an inhibin receptor and binding protein has expanded our knowledge of the mechanism whereby inhibin antagonizes activin action. Controlled experimental studies have clarified the regulation and physiology of inhibin A and inhibin B, providing evidence for their use as markers of ovarian function. Clinical studies continue to uphold the use of inhibin as a marker for ovarian cancer, but have not generally supported its use over standard prognostic markers in assisted reproductive technologies. Finally, ongoing work suggests alterations in inhibin and follistatin that may be linked to the pathophysiology of polycystic ovary syndrome. Thus, the mechanism of inhibin action and its role in normal and abnormal ovarian function continues to emerge.     

Serum activin A, inhibin A, and follistatin concentrations in preeclampsia or small for gestational age pregnancies

OBJECTIVE: To determine whether maternal serum activin A, inhibin A, and follistatin concentrations in idiopathic small for gestational age (SGA) pregnancies are similar to those in normal pregnancies or elevated as in preeclampsia. METHODS: Maternal serum activin A, inhibin A, and follistatin concentrations were determined in 1) nulliparous women with idiopathic SGA (birth weight <10th percentile; n = 18), preeclampsia (systolic blood pressure > or =140 mmHg or diastolic blood pressure > or =90 mmHg plus proteinuria > or =2+ or >0.3 g/24h; n = 22), and normotensive controls, matched for gestational age at sampling (n = 22), and 2) a longitudinal series of samples collected at five intervals throughout pregnancy from nulliparous women with idiopathic SGA (n = 19), preeclampsia (n = 22), preeclampsia plus SGA (n = 15), or who had uncomplicated pregnancies (n = 20). RESULTS: Serum concentrations of activin A and inhibin A were similar in idiopathic SGA pregnancies to controls. In preeclampsia, activin A and inhibin A levels were markedly increased compared with controls or women with idiopathic SGA (P <.001), particularly in those with early-onset disease. Follistatin concentrations were only modestly (相似文献   

Regulation of activin A, inhibin A, and follistatin production in human amnion and choriodecidual explants by inflammatory mediators

OBJECTIVE: To determine the effects of inflammatory mediators on the production of activin A, inhibin A, and the binding protein follistatin in term amnion and choriodecidual tissues. METHODS: The effects of interleukin-1 beta (IL-1 beta; 1 ng/mL), tumor necrosis factor-alpha (TNF-alpha; 10 ng/mL), and bacterial lipopolysaccharide (LPS; 5 microg/mL) on production rates of activin A, inhibin A, and follistatin by term choriodecidual and amnion membranes in explant culture were determined using specific enzyme-linked immunoabsorbent assays. RESULTS: All explants (n = 6 placentas) produced detectable amounts of activin A, inhibin A, and follistatin under basal conditions; choriodecidual production rates were more than tenfold higher than amnion rates. In amnion explants, activin A production was stimulated by IL-1 beta and TNF-alpha to 450 +/- 155.4% and 531 +/- 170.8% of control, respectively (mean +/- standard error of the mean; P <.05 by analysis of variance), whereas production of inhibin and follistatin was stimulated to a much more modest extent. Similar responses were observed in the choriodecidual explants. Lipopolysaccharide had no significant effect on amnion activin A production, but stimulated choriodecidual production to 290 +/- 34% of control. Lipopolysaccharide exerted only limited effects on inhibin A and follistatin production. CONCLUSIONS: Treatment with proinflammatory mediators resulted in a preferential increase in activin A production compared with that of inhibin A or follistatin. These findings suggest that inflammation of the gestational membranes could result in increased local activin A production and bioactivity.     

Inhibins, activins, and follistatin in the aging female and male

Dimeric inhibins, activins, and follistatin (FS) were all initially characterized as reproductive endocrine hormones that regulate follicle-stimulating hormone (FSH) secretion. This model, however, has expanded under the weight of current medical evidence. Activin appears to play a central auto/paracrine role in reproductive and nonreproductive tissues. Inhibin and FS each have important counterregulatory functions in activin signaling. With reproductive aging, inhibin B declines along with the follicular pool and disturbs the dynamics of the normal menstrual cycle of midreproductive age. The loss of inhibin restraint of FSH secretion appears to be the initiating endocrine event that leads to menstrual cycle shortening and some of the hormonal unpredictability of the late reproductive years. It may also be related to the decline in fertility that occurs in reproductive aging. In men, inhibin B is an excellent marker for gonadal competence, and the decline of inhibin B with age reflects decreased gonadal reserve in both sexes. Circulating activin increases with aging, but its effect on reproduction in women and men is not clear. FS does not appear to change greatly with aging in men or women. The age-related fluctuations in this delicately balanced regulatory triad influence reproductive capacity and the sequelae of chronological aging. Elucidation of the molecular pathways responsible for the action of these hormones may allow closer integration with their current conceptual roles in aging.     

育龄女性卵泡早期INHb、FS、ACTa血清水平与年龄的相关性

目的:探讨育龄女性内分泌激素抑制素(INHb)、卵泡抑素(FS)、激活素(ACTa)随年龄而发生的变化趋势。方法:采用双抗体夹心酶联免疫吸附技术(Sandwich ELISA),检测97名无内分泌疾病的育龄妇女月经周期d 3血清中INHb、FS、ACTa水平,并分析其与年龄的相关性。结果:INHb随年龄增长而降低(r =-0.567,P<0.01),FS随年龄增长而升高(r =0.398,P<0.05),ACTa不随年龄而变化(r =0.179,P>0.05),但ACTa/FS随年龄增长而降低(r =-0.502,P<0.05)。结论:INH-FS-ACT系统随年龄增长而有一定的变化趋势,并可预示卵巢功能的减退。     

Maternal serum activin A, inhibin A, and follistatin in pregnancies with appropriately grown and small-for-gestational-age fetuses classified by umbilical artery Doppler ultrasound

OBJECTIVE: The purpose of this study was to examine the relationship of maternal serum activin A, inhibin A, and follistatin with fetal growth and placental function. STUDY DESIGN: Inhibin A, activin A, and follistatin were measured in maternal serum that was stored from normally grown (control subjects, n = 50) and small-for-gestational-age pregnancies (n = 49), prospectively classified as normal small-for-gestational-age pregnancy or fetal growth-restricted pregnancy with the use of umbilical artery Doppler ultrasound. RESULTS: Activin A and inhibin A were significantly increased in fetal growth-restricted pregnancies compared with control subjects (activin A: regression coefficient, 0.54, P <.001; inhibin A: regression coefficient, 0.47, P =.003). The activin:follistatin ratio was significantly higher in fetal growth-restricted pregnancies compared with control subjects (P <.001). There were no significant differences between analyte levels of normal small-for-gestational-age pregnancies and control subjects. CONCLUSION: Maternal serum activin A, inhibin A, and activin:follistatin ratio are raised in fetal growth-restricted pregnancies but not in normal small-for-gestational age pregnancies. This provides further evidence of the difference between subgroups within small-for-gestational-age pregnancies and emphasizes the need to stratify for this in research.     

Impact of menopause on the augmentation of arterial stiffness with aging

BACKGROUND/AIMS: Aortic stiffness, determined by pulse wave velocity (PWV), is an independent marker of cardiovascular risk. PWV is mainly influenced by age-associated alterations in arterial wall structure and blood pressure. The present study was conducted to assess the impact of menopause on the brachial-ankle PWV (baPWV) in healthy women. METHODS: Fifty premenopausal women aged 22-54 years and 40 postmenopausal women aged 40-73 years were recruited for this study. Subjects with hypertension, diabetes, and hyperlipidemia were strictly excluded. The results of baPWV were analyzed chronologically by 10- or 5-year age intervals. RESULTS: There was no significant difference in baPWV between premenopausal and postmenopausal women in their 40s and 50s. The baPWV of postmenopausal women aged over 60 years was significantly higher than that of postmenopausal women in their 50s. To clarify the age-dependent elevation in baPWV in detail, women their 50s and 60s were divided into subgroups by 5-year age intervals. There was no significant difference in baPWV among the 50-54-, 55-59- and 60-64-year subgroups. baPWV significantly increased in the 65-69- year subgroup (p< 0.05). There was a significant relationship between baPWV and age in premenopausal (r = 0.452, p = 0.001) and postmenopausal (r = 0.581, p < 0.0001) women. The slope of the regression line for baPWV plotted against age was steeper in postmenopausal than in premenopausal women. CONCLUSIONS: This study produces suggestive evidence that menopause amplifies the age-dependent increase in arterial stiffness.     

A preliminary study comparing the endometrial expression of inhibin, activin and follistatin in women with a history of implantation failure after IVF treatment and a control group

The aim of this study was to evaluate the expression of activin: beta A and beta B subunit and follistatin in endometrium of women with implantation failure ( n = 10) and compare it with a fertile control group ( n = 7). Immunohistochemical staining intensity for follistatin in the endometrial glandular epithelium from women with implantation failure were significantly lower than that in control women ( P = 0.03). The decreased expression of follistatin in epithelial cells in the endometrium of women with implantation failure after in vitro fertilisation (IVF) may suggest that follistatin may play a role in the implantation process.     

Effects of protein kinase A and C inhibitors on follicular inhibin and activin during ovulation

Ovulation is associated with a rise in activin A and a decline in pro-alpha C, inhibin A and inhibin B secretion. It is believed that the actions of inhibin and activin during human chorionic gonadotrophin (HCG) stimulation are mediated by protein kinase A (PKA) and/or protein kinase C (PKC). Using an in-vitro murine prenatal follicle culture model, the effects of a PKA inhibitor, Rp-cAMP, and a PKC inhibitor, PKIM, on inhibin and activin gene expression, secretion, ovulation and oocyte maturation were studied during HCG stimulation. Both Rp-cAMP (0.1 micromol/l and 1.0 micromol/l) and PKIM (1.0 micromol/l) significantly (P < 0.001) inhibited the action of HCG by suppressing the increase in activin A secretion whilst preventing the decline in pro-alpha C, inhibin A and B. In addition, Rp-cAMP and PKIM were able to significantly (P < 0.05) reduce the rate of HCG-induced ovulation and meiotic resumption, but had no effect on the completion of oocyte maturation. Furthermore, HCG-induced ovulation resulted in the reduction of all three inhibin subunits, but inhibin subunit expression was not affected by Rp-cAMP and PKIM. These results provide evidence supporting a role for PKA and PKC pathways in the signalling mechanism for inhibin and activin action during ovulation and meiotic resumption of the oocyte.     

Long-term effects of the menopause and sex hormones on skin thickness

Skin collagen content and skin thickness in a group of postmenopausal women who had been treated with sex hormone implants were compared with those in an untreated group of similar women. Both skin collagen content and thickness were found to be significantly greater in the treated than in the untreated group. In the untreated women skin collagen content declined in relation to menopausal age but not to chronological age. No correlation was found with menopausal age, chronological age or duration of therapy in the treated group. These data suggest that skin collagen is influenced by the sex hormone status and declines after the menopause, contributing to the increase in urinary hydroxyproline excretion that has been reported to occur at this time.