Insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 in women with premenstrual syndrome

Objective: To determine whether women with premenstrual syndrome (PMS) have aberrations of the GH axis as has been demonstrated in individuals with depression.

Design: Prospective trial.

Setting: Department of Obstetrics and Gynecology, University of California, Los Angeles.

Patient(s): After prospective screening, 32 healthy women with PMS and 32 asymptomatic controls completed the study.

Intervention(s): Subjects completed a daily PMS symptom diary and a Beck Depression Inventory. They underwent phlebotomy 5 days and 12 days after the LH midcycle surge, which was identified with the use of a urinary LH detection kit.

Main Outcome Measure(s): Serum levels of insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein-3 (IGFBP-3), E₂, and progesterone.

Result(s): Levels of IGF-1, IGFBP-3, E₂, and progesterone did not differ between women with prospectively documented PMS and control subjects.

Conclusion(s): Premenstrual syndrome and affective disorder share common symptoms and possibly a common cause. Biochemical markers such as alterations in the somatotropic system often are associated with major depression. Levels of IGF-1 and IGFBP-3 did not differ between women with PMS and control subjects, supporting the concept that PMS and endogenous depression are biologically distinct entities.     

Insulin-like growth factor-binding protein PP12 in ovarian cyst fluid

Summary Elevated levels of insulin-like growth factor-binding protein (IGF-bp) were recently found in the serum of patients with ovarian tumors. We studied the concentration of IGF-bp in cyst fluids of 37 women operated on for benign or malignant ovarian cysts. The levels were elevated (>47 g/l) in 6 of 28 benign, but in none of the nine malignant ovarian cysts. The highest IGF-bp concentration (447 g/l) was observed in a benign serous cystadenoma.     

胰岛素样生长因子及胰岛素样生长因子结合蛋白-3与胎儿生长受限的关系

目的　探讨胰岛素样生长因子 (IGF) Ⅰ、IGF Ⅱ和IGF结合蛋白 3(IGFBP 3)与胎儿生长的关系 ,以及IGF在胎儿生长受限 (FGR)发病中的作用。方法　选取 2 0例分娩FGR胎儿 (FGR组 )、10例分娩巨大儿 (巨大儿组 )及 2 0例分娩正常儿 (对照组 )的产妇 ,抽取 3组产妇分娩后肘静脉血及其新生儿脐静脉血 ,分离血清。采用放射免疫法和免疫放射法测定 3组产妇及其新生儿血清中IGF Ⅰ、IGF Ⅱ及IGFBP 3的水平。结果　 (1)FGR组产妇血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为(130 5± 2 6 0 ) μg/L、(2 40± 0 42 ) μg/L及(5 5 79± 848) μg/L ;新生儿脐血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (6 6± 1 7) μg/L、(1 5 4± 0 31) μg/L及 (86 9± 183) μg/L。 (2 )巨大儿组产妇血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (30 9 7± 44 6 ) μg/L、(2 43± 0 2 5 ) μg/L及(5 5 6 2± 742 ) μg/L ;新生儿脐血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (6 9 6± 2 3 9) μg/L、(2 19± 0 2 9) μg/L及(16 82± 130 )μg/L。(3)对照组产妇血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (30 7 9± 70 7) μg/L、(2 41± 0 36 )μg/L及 (5 5 86± 6 78) μg/L ;新生儿脐血清IGF Ⅰ、IGF Ⅱ及IGFBP 3水平分别为 (6 8 9     

Insulin-like growth factor-binding protein-1 in cervical secretion as a predictor of preterm delivery

BACKGROUND: The aim of the study was to evaluate whether the phosphorylated isoforms of insulin-like growth factor-binding protein-1 (IGFBP-1), a protein produced by the decidua, can be detected in cervical secretions of pregnant women with preterm uterine contractions, and whether their presence predicts an increased risk of preterm delivery. METHODS: A prospective analysis of sixty-three women who presented with preterm labor but intact fetal membranes at weeks 22-36+6 days of gestation at the Antenatal clinic at the Department of Obstetrics and Gynecology, Helsinki University Central Hospital. Phosphorylated IGFBP-1 (phIGFBP-1) was measured in cervical swab samples obtained at presentation, using an immunoenzymometric assay. The values > or =10 microg/L were considered as positive. In addition, 58 asymptomatic women at the same gestational stage were studied as controls. Multiple logistic regression was applied to control for confounding variables and to obtain adjusted odds ratios. RESULTS: The concentration of phIGFBP-1 in cervical samples ranged from undetectable to 95 microg/L. In 17 of the 63 (27%) women with preterm labor it was > or =10 microg/L. Seven of these 17 (41%) women with a positive phIGFBP-1 result delivered preterm, all before 35 weeks of gestation. Among the women with preterm labor and a negative phIGFBP-1 result, three of the 46 (7%) delivered before 37 weeks of gestation (adjusted OR 24, 95% CI 1.2-487), but all after 35 weeks of gestation. In the asymptomatic control population three out of 58 (5%) women had a positive cervical phIGFBP-1 test result but none delivered preterm. Among the controls with a negative cervical phIGFBP-1 test result (55 of 58, 95%), one woman delivered preterm (1 of 55, 2%). CONCLUSIONS: Pregnant women who are in preterm labor with intact fetal membranes and who have a positive phIGFBP-1 test result in cervical secretion have an increased risk of preterm delivery.     

Immunohistochemical localization of insulin-like growth factor-binding protein-3 in eutopic and ectopic endometrial tissues

Objective: To evaluate the expression of insulin-like growth factor–binding protein-3 (IGFBP-3) in the eutopic endometrium and in endometriotic lesions.

Design: Retrospective immunohistochemical study.

Patient(s): Twenty-five normal women and 39 women with endometriosis.

Intervention(s): Endometrial and endometriotic tissue biopsies obtained at laparoscopy.

Main Outcome Measure(s): Expression of IGFBP-3 assessed by immunohistochemistry.

Result(s): In the endometrium, positive immunostaining of IGFBP-3 was observed both in the stroma and the epithelial glands. The intensity of staining in the glands during the secretory phase was significantly higher in women with endometriosis compared with controls (P=.018). An increased expression of IGFBP-3 over controls was found in stages I and II of the disease (P=.018), whereas in stages III and IV, the difference between controls and women with endometriosis was not significant (P=.300). In endometriotic tissues, a much-marked immunostaining of IGFBP-3 was noted in 90% of the glands and 67% of the stroma without apparent differences related to cycle phase.

Conclusion(s): These data show intense staining of IGFBP-3 in endometriosis lesions and increased expression of the protein in the endometrium of patients with endometriosis compared to controls. This marked expression of IGFBP-3 could be related to its previous finding in the peritoneal fluid and to its potential involvement in the pathophysiology of endometriosis.     

Insulin-like growth factor-1 and insulin-like growth factor binding protein-1 and 3 in the follicular fluid of infertile patients submitted to in vitro fertilization

Purpose: In the present article we propose to evaluate IGF-1, IGFBP-1 and 3 in the follicular fluid of infertile patients submitted to in vitro fertilization.Methods: We performed a case-control study with 53 infertile patients submitted to the first in vitro fertilization attempt. We compared their follicular fluid concentration of IGF-1, IGFBP-1 and IGFBP-3 between the patients who became pregnant (n = 11) versus those nonpregnant (n = 42).Results: The clinical characteristics of patients from the two groups were similar in terms of age and body mass index. Data related to the analysis of ovulation induction was not different regarding length of induction in days, number of retrieved oocytes, fertilization rate, and number of transferred embryos. Furthermore, the number of FSH units required for ovarian induction was also similar between the studied groups.IGF-1 and IGFBP-1 were not significantly different between the groups (p > 0.05). However, those patients that became pregnant presented a lower follicular fluid concentration of IGFBP-3, 2237.10 ± 582.73 pg/ml and 2657.64 ± 584.15 ng/ml, respectively (p = 0.038).Conclusions: We demonstrated an association of a lower follicular fluid IGFBP-3 in individuals that became pregnant compared to subjects that did not after in vitro fertilization.     

Insulin-like growth factor-binding protein-1 (IGFBP-1) in cervical secretions as a predictor of preterm delivery.

OBJECTIVE: The objective of this study was to investigate the level of insulin-like growth factor-binding protein-1 (IGFBP-1) in cervical secretions and Bishop score as predictors of preterm delivery in asymptomatic pregnant women. METHODS: This was a prospective study at the Clinic for Gynecology and Obstetrics at the University Clinical Center in Tuzla, on a sample of 80 healthy pregnant women at between 24 and 34 gestational weeks. After interview every woman underwent IGFBP-1 concentration measurement by the 'Actim Partus' test. The Bishop score was determined by the author (A.L) during vaginal examination. Rates among groups were compared using arithmetic mean and standard deviation, Student's t-test, Mann-Witney U-test, and Spearman-Rank correlation test. Statistical importance was determined at the variation levels of 5% and 1%. RESULTS: Eight (10.00%) women in the study group had a positive Actim Partus test and six (7.50%) of them had a preterm delivery. The positive predictive value was 44.44% and negative predictive value was 98.59%. The specificity of the Bishop score in the study group was 83.78% and the sensitivity was 50.00%. The positive predictive value of the Bishop score in this group was 20.00% and the negative predictive value was 95.36%. There was no correlation between the Bishop score and Actim Partus test (p = 0.15). CONCLUSIONS: If the concentration of IGFBP-1 is <10 microg/L (negative Actim Partus test) in asymptomatic pregnant women, the risk of preterm delivery is low. The Actim Partus test could be used as a screening test for preterm delivery in asymptomatic pregnant women.     

Human chorionic gonadotropin inhibits insulin-like growth factor-binding protein-1 and prolactin in decidualized human endometrial stromal cells

Recent data clearly show that hCG, as one of the first hormonal signals of the embryo, is involved in the modulation of endometrial receptivity in the secretory phase. Here we report a significant dose- and time-dependent inhibition of insulin-like growth factor-binding protein-1 and prolactin by hCG in human endometrial stromal cells after decidualization in vitro-findings that further underline the role of hCG in the endometrial milieu during early implantation.     

IGFBP-7在子宫内膜腺癌中的表达及其意义

目的:研究胰岛素样生长因子结合蛋白7(IGFBP-7)在子宫内膜腺癌组织的表达,并分析其与子宫内膜样腺癌临床病理参数之间的关系。方法:选取2011年1月~2012年12月郑州大学第一附属医院病理科存档的手术切除石蜡包埋子宫内膜组织标本共123例,其中子宫内膜样腺癌61例,子宫内膜非典型增生22例,子宫内膜简单性增生10例,正常子宫内膜组织30例。免疫组化SP法检测IGFBP-7的表达,实时荧光定量RT-PCR法检测IGFBP-7 mRNA的表达。分析IGFBP-7的阳性表达率与子宫内膜样腺癌临床病理参数之间的关系。结果:(1)免疫组化法检测显示,子宫内膜样腺癌组织中的IGFBP-7阳性表达率显著高于子宫内膜非典型增生和子宫内膜简单性增生(P0.05);IGFBP-7的表达与子宫内膜癌的病理分级、超重、合并高血压、合并糖尿病有关(P0.05);(2)RT-PCR检测结果显示,子宫内膜样腺癌中IGFBP7 mRNA表达量显著高于子宫内膜非典型增生、简单性增生和正常子宫内膜组织(P0.01)。结论:IGFBP-7基因可能参与了子宫内膜腺癌的发生发展过程。     

The relationship between insulin and insulin-like growth factor binding protein-1 is modified by pre-eclampsia

Insulin is the main negative regulator of insulin-like growth factor binding protein-1 (IGFBP-1) in the non-pregnant state. Although changes in insulin resistance and circulating level of IGFBP-1 occur in pre-eclampsia, little is known about the relationship between insulin and IGFBP-1 in pregnancies complicated by the disease. In this study, we have investigated whether the relationship between insulin and IGFBP-1 is modified by pre-eclampsia. Maternal levels of insulin and IGFBP-1 were measured, at 4-weekly intervals between 16 and 36 weeks' gestation, in plasma samples obtained from ten normal pregnant controls and ten women who developed pre-eclampsia. The controls were chosen to be similar in maternal age and booking body mass index to the pre-eclampsia group. Insulin levels increased in both the normal controls and the women who developed pre-eclampsia. The levels in pre-eclampsia were significantly greater than those in normal pregnancy at 32 and 36 weeks' gestation (p?=?0.02 and 0.005, respectively). IGFBP-1 levels were unchanged in normal pregnancy and rose in pre-eclampsia. In normal pregnancy, insulin levels were inversely related to IGFBP-1 levels throughout. In women developing pre-eclampsia, the relationship between insulin and IGFBP-1 was negative at 16 weeks and positive from 24 weeks. These data suggest that whereas the inverse relationship between insulin and IGFBP-1 is maintained during normal pregnancy, this relationship is reversed in women who develop pre-eclampsia.     

Serum levels of leptin,insulin-like growth factor-I and insulin-like growth factor binding protein-3 in women with pre-eclampsia,and their relationship to insulin resistance

The present study was carried out to compare serum levels of leptin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3), homeostasis model assessment–(pancreatic β-cell function) (HOMA-(%B)) and homeostasis model assessment–(tissue insulin sensitivity) (HOMA-(%S)) in women with mild and severe pre-eclampsia and normotensive pregnant women; and to evaluate the possible relationships between these parameters in the pathogenesis of pre-eclampsia. Seventy-three women were divided into three groups: group A consisted of 20 normotensive pregnant women (NPW); group B consisted of 25 women with mild pre-eclampsia (MPE); and group C consisted of 28 women with severe pre-eclampsia (SPE). Serum level of leptin was measured by enzyme immunoassay using a commercial kit. Serum levels of IGF-I and IGFBP-3 were measured with a two-site immunoradiometric assay. Serum level of insulin was measured by the electrochemiluminescence immunoassay method. HOMA used indices of pancreatic β-cell function and tissue insulin sensitivity. Differences between groups were compared by one-way analyses of variance and the post hoc Tukey–HSD test for multiple comparisons; however, when a variable was not normally distributed, the Mann–Whitney U test was used. Associations between variables were tested using Pearson's coefficient of correlation. Birth weight was significantly lower (p?<?0.001) in the MPE and SPE groups than in the NPW group. Serum levels of leptin and insulin in women with SPE and MPE were significantly higher (p?<?0.001) than in NPW. Serum levels of IGF-I and IGFBP-3 were significantly lower in women with SPE and MPE compared with NPW (p?<?0.001). The mean HOMA-(%B) level in women with SPE and MPE was significantly higher than in NPW (p?<?0.001), whereas the mean HOMA-(%S) level in women with SPE and MPE was significantly lower than in NPW (p?<?0.001). In the SPE group, systolic blood pressure correlated significantly with serum levels of IGF-I and leptin (r?=?0.375, p?<?0.05 and r?= 0.495, p?<?0.01, respectively). A negative correlation between mean HOMA-(%S) level and serum IGFBP-3 level was noted (r?=?–0.357, p?<?0.05). There was a positive correlation between serum level of IGF-I and mean HOMA-(%B) level in mildly pre-eclamptic women (r?=?0.541, p?<?0.01). We conclude that pre-eclampsia is associated with insulin resistance; and that existing hyperinsulinemia and insulin resistance in women with pre-eclampsia seem not to correlate with leptin and birth weight, but may correlate positively with IGF-1 and IGFBP-3. Therefore we think that hyperleptinemia, low IGF-I or IGFBP-3, and insulin resistance may contribute to the pathogenesis of pre-eclampsia.     

胰岛素样生长因子1及胰岛素样生长因子结合蛋白3与胎儿生长发育的关系

目的:探讨胰岛素样生长因子1（IGF-1）及胰岛素样生长因子结合蛋白3（IGFBP-3）与胎儿生长发育的关系。方法:应用酶联免疫吸附试验（LISA）测定26例正常妊娠（正常组）,42例妊娠期糖尿病（GDM组）,20例胎儿宫内发育迟缓（IUGR组）孕妇足月剖宫产分娩时,母血与脐血中IGF-1及IGFBP-3的水平,同时记录3组孕妇的新生儿出生体重。结果:（1）母血IGF-1及IGFBP-3的水平正常组分别为18 6.81μg/L、22.82μg/L,GDM组为283.35μg/L、28.29μg/L,IUGR组为220.64μg/L、25.23μg/L,3组间 IGF-IN IGFBP.3水平差异均无显著性（P>0.05）;（2）脐血IGF-1及IGFBP-3的水平正常组分别为62.54μg/L、8.56μg/L,GDM组分别为83.74μg/L、10.21μg/L,IUGR组为37.94μg/L、7.82μg/L,分别进行3组间两两比较,3组IGF-1及IGFBP-3的差异均有显著性（P<0.01）;（3）新生儿平均出生体重正常组为3.22±0.32kg,GDM组为3.76±0.43kg,IUGR组为2.41±0.17kg,3组间两两比较,差异均有显著性（P<0.01）;（4）3组脐血IGF-1及IGFBP-3水平与新生儿出生体重均有显著性正相关（P<0.01）;（5）3组母血及脐血的IGF-1与IGFBP-3均呈显著性正相关（P<0.01）。结论:来自胎儿循环的IGF-1、IGFBP-3对胎儿的生长发育有重要的调节作用,可能参与巨大儿及IUGR的病     

The relationship between insulin and insulin-like growth factor binding protein-1 is modified by pre-eclampsia.

Insulin is the main negative regulator of insulin-like growth factor binding protein-1 (IGFBP-1) in the non-pregnant state. Although changes in insulin resistance and circulating level of IGFBP-1 occur in pre-eclampsia, little is known about the relationship between insulin and IGFBP-1 in pregnancies complicated by the disease. In this study, we have investigated whether the relationship between insulin and IGFBP-1 is modified by pre-eclampsia. Maternal levels of insulin and IGFBP-1 were measured, at 4-weekly intervals between 16 and 36 weeks' gestation, in plasma samples obtained from ten normal pregnant controls and ten women who developed pre-eclampsia. The controls were chosen to be similar in maternal age and booking body mass index to the pre-eclampsia group. Insulin levels increased in both the normal controls and the women who developed pre-eclampsia. The levels in pre-eclampsia were significantly greater than those in normal pregnancy at 32 and 36 weeks' gestation (p = 0.02 and 0.005, respectively). IGFBP-1 levels were unchanged in normal pregnancy and rose in pre-eclampsia. In normal pregnancy, insulin levels were inversely related to IGFBP-1 levels throughout. In women developing pre-eclampsia, the relationship between insulin and IGFBP-1 was negative at 16 weeks and positive from 24 weeks. These data suggest that whereas the inverse relationship between insulin and IGFBP-1 is maintained during normal pregnancy, this relationship is reversed in women who develop pre-eclampsia.     

Serum levels of leptin, insulin-like growth factor-I and insulin-like growth factor binding protein-3 in women with pre-eclampsia, and their relationship to insulin resistance.

The present study was carried out to compare serum levels of leptin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3), homeostasis model assessment--(pancreatic beta-cell function) (HOMA-(%B)) and homeostasis model assessment--(tissue insulin sensitivity) (HOMA-(%S)) in women with mild and severe pre-eclampsia and normotensive pregnant women; and to evaluate the possible relationships between these parameters in the pathogenesis of pre-eclampsia. Seventy-three women were divided into three groups: group A consisted of 20 normotensive pregnant women (NPW); group B consisted of 25 women with mild pre-eclampsia (MPE); and group C consisted of 28 women with severe pre-eclampsia (SPE). Serum level of leptin was measured by enzyme immunoassay using a commercial kit. Serum levels of IGF-I and IGFBP-3 were measured with a two-site immunoradiometric assay. Serum level of insulin was measured by the electrochemiluminescence immunoassay method. HOMA used indices of pancreatic beta-cell function and tissue insulin sensitivity. Differences between groups were compared by one-way analyses of variance and the post hoc Tukey-HSD test for multiple comparisons; however, when a variable was not normally distributed, the Mann-Whitney U test was used. Associations between variables were tested using Pearson's coefficient of correlation. Birth weight was significantly lower (p < 0.001) in the MPE and SPE groups than in the NPW group. Serum levels of leptin and insulin in women with SPE and MPE were significantly higher (p < 0.001) than in NPW. Serum levels of IGF-I and IGFBP-3 were significantly lower in women with SPE and MPE compared with NPW (p < 0.001). The mean HOMA-(%B) level in women with SPE and MPE was significantly higher than in NPW (p < 0.001), whereas the mean HOMA-(%S) level in women with SPE and MPE was significantly lower than in NPW (p < 0.001). In the SPE group, systolic blood pressure correlated significantly with serum levels of IGF-I and leptin (r = 0.375, p < 0.05 and r = 0.495, p < 0.01, respectively). A negative correlation between mean HOMA-(%S) level and serum IGFBP-3 level was noted (r = -0.357, p < 0.05). There was a positive correlation between serum level of IGF-I and mean HOMA-(%B) level in mildly pre-eclamptic women (r = 0.541, p < 0.01). We conclude that pre-eclampsia is associated with insulin resistance; and that existing hyperinsulinemia and insulin resistance in women with pre-eclampsia seem not to correlate with leptin and birth weight, but may correlate positively with IGF-1 and IGFBP-3. Therefore we think that hyperleptinemia, low IGF-I or IGFBP-3, and insulin resistance may contribute to the pathogenesis of pre-eclampsia.