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.     

脂源性细胞因子与子痫前期关系的研究

目的:探讨子痫前期(PE)患者血清脂源性细胞因子(脂联素和瘦素)水平的变化及其意义。方法:以53例子痫前期孕妇为研究组(其中轻度子痫前期32例、重度子痫前期21例),20例同期分娩的正常孕妇为对照组。采用ELISA法检测血清脂联素和瘦素水平。同时检测血清甘油三脂(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平。结果:(1)轻度、重度子痫前期患者血清脂联素水平分别为8.88±4.67μg/m l及5.14±2.79μg/m l,明显低于对照组11.61±2.90μg/m l,差异有统计学意义(P<0.01)。而轻度、重度子痫前期患者血清瘦素水平为21.79±15.19ng/m l及27.27±18.38ng/m l,明显高于对照组的12.35±6.51ng/m l,差异有统计学意义(P<0.05,P<0.01),(2)子痫前期患者血清脂联素与TG、TC、LDL-C、HDL-C均显著相关(r分别为-0.658、-0.624、-0.419、0.461),瘦素水平也与上述指标显著相关(r分别为0.534、0.707、0.418、-0.513),(3)子痫前期患者血清脂联素及瘦素水平呈高度负相关(r=-0.760,P<0.01)。结论:脂联素、瘦素等脂源性细胞因子在PE的发病中可能起一定的作用。     

Serum insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3, leptin concentrations and insulin resistance in benign and malignant epithelial ovarian tumors in postmenopausal women.

AIMS: The aims of the present study were to determine the serum concentrations of insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and leptin and insulin resistance in benign and malignant epithelial ovarian tumors, and to discuss the use of these markers in benign-malignant tumor differentiation. METHODS: Forty-seven postmenopausal women with ovarian tumor and 31 age-matched, postmenopausal, healthy controls were included in this study. Insulin resistance index by homeostasis model assessment (HOMA score) and fasting blood glucose (FBG), serum IGF-I, IGFBP-3, leptin and CA-125 concentrations were determined in all patients preoperatively. The results were evaluated according to postoperative histopathology results. RESULTS: According to postoperative histopathology results, the patients were divided into malignant (n = 23), benign (n = 24) and control (n = 31) groups. There were no differences among the groups in relation to age, body mass index, FBG and HOMA score (p > 0.05). Serum concentrations of CA-125 were elevated in the malignant group compared with the benign ovarian tumor and control groups (p < 0.05). In contrast, serum IGF-I concentrations were significantly decreased in patients with malignant and benign ovarian tumors compared with controls (p < 0.05). Serum IGFBP-3 concentrations were also found to be lower in women with malignant ovarian tumors than in women with benign tumors (p < 0.05). Serum leptin did not differ among patients with malignant-benign tumors and controls (p > 0.05). CONCLUSION: Serum leptin and HOMA score have not been found to be valid indicators in ovarian tumors. However, the present data suggest that low concentrations of IGF-I and IGFBP-3 could be a reliable marker to differentiate benign from malignant ovarian tumors. Further experimental studies are warranted to understand the impact of the IGF-I system in ovarian carcinogenesis.     

The relationship between plasma levels of leptin and androgen in healthy and preeclamptic pregnant women

BACKGROUND: To clarify the role of leptin and androgens in the pathogenesis of preeclampsia, we wanted to assess role of maternal leptin in women with severe and mild preeclampsia and the effects of sex steroid hormones on leptin production. METHODS: The groups consisted of 40 healthy pregnant women (HPW) as well as 55 pregnant women with severe preeclampsia (SPE) and 41 pregnant women with mild preeclampsia (MPE). No significant differences were observed between the three groups regarding age, gestational age and body mass index (BMI). Plasma leptin, total testosterone (T), estradiol (E(2)), dehydroepiandrosterone sulfate (DHEAS) and androstenedione (A) levels were measured. Statistical analysis was achieved with one-way analysis of variance (anova) followed by post hoc multiple comparisons with the Tukey honestly significant difference (HSD) test by using SPSS for Windows statistical computer program, and the Pearson's coefficient of correlation was calculated. RESULTS: The plasma level of leptin was significantly increased in the SPE and MPE groups (p < 0.001), whereas the plasma level of T was significantly increased only in the SPE group (p < 0.001). However, there was no significant difference in plasma levels of DHEAS among the three groups (p < 0.05). The plasma level of A was significantly decreased in the MPE group (p < 0.05). There was no significant difference in the plasma level of E(2) in the MPE and SPE groups (p < 0.05). There was a significant positive correlation between the plasma levels of leptin and E(2) in the MPE group (r = 0.41, p < 0.001). CONCLUSION: We concluded that the elevated plasma levels of leptin and testosterone could contribute to the endothelial dysfunction involved in the pathogenesis of preeclampsia, and that estradiol might lead to an increase in the plasma levels of leptin.     

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.     

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 insulin, insulin-like growth factor-I, and insulin-like growth factor binding protein-1 in women who develop preeclampsia

OBJECTIVE: To determine whether second-trimester serum concentrations of insulin, insulin-like growth factor-I (IGF-I), and insulin-like growth factor binding protein-1 (IGFBP-1) were altered in women before they developed clinical signs of preeclampsia. METHODS: A nested case-control study used serum obtained during second-trimester pregnancies from 12 women who developed preeclampsia matched with 24 controls who remained normotensive. Nine preeclamptic subjects and 18 controls were necessary to have 80% power to discern a 20% difference between groups with regard to the analytes under consideration. RESULTS: There were no significant differences between cases and controls with respect to many demographic factors. Women who developed preeclampsia had insulin concentrations that were not significantly different from controls, but serum concentrations of IGF-I were significantly higher and IGFBP-1 were significantly lower than those of the controls. The IGF-I/IGFBP-1 ratio helped to identify those at risk for developing preeclampsia. CONCLUSIONS: Serum concentrations of IGF-I and IGFBP-1 were abnormal long before women manifested clinical evidence of preeclampsia in this study. These alterations might be related to abnormalities in trophoblastic invasion and prove useful as potential markers for the identification of women who are at high risk of developing preeclampsia.     

Serum insulin-like growth factor (IGF)-I,IGF binding protein (IGFBP)-3, leptin concentrations and insulin resistance in benign and malignant epithelial ovarian tumors in postmenopausal women

Aims. The aims of the present study were to determine the serum concentrations of insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and leptin and insulin resistance in benign and malignant epithelial ovarian tumors, and to discuss the use of these markers in benign–malignant tumor differentiation.

Methods. Forty-seven postmenopausal women with ovarian tumor and 31 age-matched, postmenopausal, healthy controls were included in this study. Insulin resistance index by homeostasis model assessment (HOMA score) and fasting blood glucose (FBG), serum IGF-I, IGFBP-3, leptin and CA-125 concentrations were determined in all patients preoperatively. The results were evaluated according to postoperative histopathology results.

Results. According to postoperative histopathology results, the patients were divided into malignant (n = 23), benign (n = 24) and control (n = 31) groups. There were no differences among the groups in relation to age, body mass index, FBG and HOMA score (p > 0.05). Serum concentrations of CA-125 were elevated in the malignant group compared with the benign ovarian tumor and control groups (p < 0.05). In contrast, serum IGF-I concentrations were significantly decreased in patients with malignant and benign ovarian tumors compared with controls (p < 0.05). Serum IGFBP-3 concentrations were also found to be lower in women with malignant ovarian tumors than in women with benign tumors (p < 0.05). Serum leptin did not differ among patients with malignant–benign tumors and controls (p > 0.05).

Conclusion. Serum leptin and HOMA score have not been found to be valid indicators in ovarian tumors. However, the present data suggest that low concentrations of IGF-I and IGFBP-3 could be a reliable marker to differentiate benign from malignant ovarian tumors. Further experimental studies are warranted to understand the impact of the IGF-I system in ovarian carcinogenesis.     

Concentrations of insulin-like growth factor (IGF)-I and IGF binding protein-3 in the follicular fluid of women undergoing ovarian hyperstimulation with different gonadotropin preparations.

Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) have an important regulatory role in follicular development and oocyte maturation. The aim of this prospective, randomized, double-blind study was to measure the concentrations of IGF-I and IGFBP-3 in follicular fluids collected from infertile women undergoing ovarian hyperstimulation using three different gonadotropin preparations. Twenty infertile women (mean age 33 years, range 28-40) undergoing in vitro fertilization (IVF) programs were recruited. After a written informed consent, each woman randomly underwent a long-protocol for ovarian hyperstimulation using gonadotropin-releasing hormone (GnRH)-analog and one of the following recombinant- and urinary-gonadotropins--alpha-follitropin, beta-follitropin or urofollitropin. Serum 17 beta-estradiol (E2) levels and follicle growth were assessed during the follicular phase. The concentrations of IGF-I and IGFBP-3 in the follicular fluid of aspirated dominant follicles were measured directly. Women treated with alpha-follitropin needed significantly lower doses of follicle-stimulating hormone (FSH) compared to those receiving beta-follitropin (p < 0.05). No other statistically significant differences were detected between groups. Serum E2 levels increased in the three groups from early to late follicular phase. Follicular fluid IGF-I and IGFBP-3 concentrations did not differ significantly in the three groups of women. A statistically significant relationship was observed between follicular fluid IGF-I and IGFBP-3 levels (r = 0.41, p = 0.001). Oocyte maturation correlated in a positive manner with IGF-I (r = 0.34, p = 0.01) and IGFBP-3 (r = 0.29, p = 0.03). These findings show that both recombinant- and urinary-gonadotropin preparations were equally effective in releasing IGF-I and IGFBP-3 in the follicular fluid of dominant follicles, and confirmed the role of these compounds on oocyte maturation.     

Changes in serum levels of leptin, cytokines and lipoprotein in pre-eclamptic and normotensive pregnant women.

The aim of this study was to investigate the changes in serum levels of leptin, cytokines and lipoproteins in women with pre-eclampsia and to evaluate their clinical significance in the pathogenesis of pre-eclampsia. We performed a prospective study involving 45 women with pre-eclampsia in the third trimester of pregnancy and 30 normotensive women in the third trimester of pregnancy. Serum level of leptin was measured by enzyme immunoassay using a Cayman chemical kit. Serum levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, soluble IL-2 receptor (slL-2R), IL-6 and IL-8 were measured by using a non-radioimmunoassay chemiluminescent method. Serum lipid concentrations were measured by an Abbott Aeroset (USA) autoanalyzer. Serum levels of apolipoprotein (Apo)A-I and ApoB were evaluated by nephelometrics assays. Differences between groups were evaluated with Student's unpaired t test and, when a variable was not normally distributed, the Mann-Whitney U test was used. The relationship between the variable was explored by the Pearson correlation test. Serum levels of leptin, TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 in the pre-eclamptic women were significantly higher than in normotensive women (p < 0.001). In the pre-eclamptic women serum levels of triglycerides, total cholesterol and low-density lipoprotein (LDL)-cholesterol were significantly increased (p < 0.001), while high-density lipoprotein (HDL)-cholesterol and Apo-A were significantly decreased compared to levels in normotensive pregnant women (p < 0.001). No significant differences were noted between the groups in Apo-B (p > 0.05). Serum levels of TNF-alpha were significantly correlated with the serum levels of IL-6, IL-8, triglycerides, sIL-2R, Apo-A and hematocrit in pre-eclamptic women (r = 0.418, p < 0.05; r= 0.389, p < 0.01; r=0.312, p < 0.05; r= -0.318, p < 0.05; r= -0.340, p < 0.05 and r=0.41, p < 0.01, respectively). A negative correlation was seen between serum level of leptin and both IL-1beta and Apo-A in pre-eclamptic women (r=-0.44, p < 0.05; r=-0.39, p < 0.05, respectively). Serum levels of IL-6 were also significantly correlated with the serum levels of HDL-cholesterol, LDL-cholesterol and body mass index (BMI) in pre-eclamptic women (r=0.40, p < 0.01; r=-0.568, p < 0.01; r= -0.30, p < 0.05, respectively). In addition, serum level of IL-8 were significantly correlated with the serum levels of HDL-cholesterol, total cholesterol and BMI in pre-eclamptic women (r= 0.368, p < 0.05; r=0.513, p < 0.01 and r= -0.41, p < 0.01, respectively). We found that the pre-eclampsia associated with increases in serum levels of leptin, TNF-alpha, cytokines, triglycerides, total cholesterol and LDL-cholesterol was associated with a significant reduction in serum levels of HDL-cholesterol and Apo-A. These association may be due to the abnormal lipid metabolism and immune activation involved in the pathogenesis of this disease.     

Metformin therapy increases insulin-like growth factor binding protein-1 in hyperinsulinemic women with polycystic ovary syndrome

OBJECTIVES: Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, insulin resistance, compensatory hyperinsulinemia, and increased levels of free insulin-like growth factor-I (IGF-I), presumably due to a decline in IGF binding protein 1 (IGFBP-1). This study was designed to evaluate effects of metformin therapy on serum levels of IGFBP-1 and IGF-I. STUDY DESIGN: Twenty-seven obese, hyperandrogenic PCOS women with elevated fasting insulin were treated for 12 weeks with metformin (500 mg p.o., t.i.d.). Serum levels of insulin, testosterone, sex hormone binding globulin (SHBG), IGF-I, and IGFBP-1 were measured before and after treatment. Body mass index (BMI) and waist-to-hip ratio (WHR) were assessed at baseline and at the end of therapy. RESULTS: Metformin therapy significantly increased IGFBP-1 concentration by 38% (P = 0.05) but had no demonstrable effect on the total IGF-I levels. Fasting insulin levels declined by 38% (P = 0.0001) while the glucose/insulin ratio increased by 72% (P = 0.0001) and quantitative insulin sensitivity check index (QUICKI) increased by 8% (P = 0.0001). Metformin treatment also significantly decreased testosterone (by 37%, P = 0.0001) and increased SHBG concentration (by 16%, P = 0.04). Multiple linear regression analysis revealed that baseline IGFBP-1 levels correlated inversely and independently with two baseline parameters: WHR (P = 0.003) and free testosterone index (P = 0.04). CONCLUSIONS: The present study shows that metformin therapy not only restores normal levels of insulin and testosterone, but also decreases the pool of free-bioactive IGF-I by increasing the levels of circulating IGFBP-1. We provide further arguments in favor of metformin therapy in hyperinsulinemic women with PCOS.     

Serum levels of insulin, IGF-1, and IGFBP-1 in pre-eclampsia and eclampsia.

OBJECTIVES: To investigate whether the serum concentrations of insulin, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-1 (IGFBP-1) were altered in women with mild pre-eclampsia, severe pre-eclampsia, and eclampsia. METHODS: In this prospective study, we investigated 20 mild pre-eclamptic, 20 severe pre-eclamptic, and 20 eclamptic patients in the third trimester. The control group consisted of 20 healthy pregnant women. Serum levels of insulin, IGF-1, and IGFBP-1 were measured. RESULTS: In patients with eclampsia, serum levels of IGF-1 were lower, and IGFBP-1 were higher, respectively, than control and other study groups (P<0.001) The values of IGF-1 in mild pre-eclampsia and severe pre-eclampsia were lower compared with control groups (both P<0.01), but there were no differences between mild and severe pre-eclampsia. The serum levels of IGFBP-1 in severe pre-eclampsia were higher compared with control groups (P<0.01), but there was no statistical difference between mild pre-eclampsia and other groups. CONCLUSIONS: IGF-1 was lower, and IGFBP-1 was higher in pre-eclamptic and eclamptic patients than controls, these alterations were related to the severity of pre-eclampsia.     

胰岛素样生长因子I及其结合蛋白1对超排卵周期卵泡发育的影响

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Insulin-like growth factor-binding protein 1 and insulin-like growth factor-binding protein 3 in pre-eclampsia

Objective To investigate circulating levels of insulin-like growth factor-binding protein 1 (IGFBP-1) and IGFBP-3 in the mother and the fetus in pregnancies complicated by pre-eclampsia, and the relationship between serum levels of IGFBPs and fetal birthweight.
Design A prospective study over an 18 month period.
Setting A tertiary care academic medical centre.
Participants Sixty-six pregnant women with pre-eclampsia (35 cases of mild/moderate pre-eclampsia and 31 cases of severe pre-eclampsia) and 78 nonpra-eclamptic pregnant women of matched gestational weeks and maternal ages.
Main outcome measures Serum concentrations of IGFBP-1 and IGFBP-3 at the time of delivery.
Results In pre-eclampsia associated with intrauterine growth retardation (IUGR), maternal and cord serum IGFBP-1 levels at the time of delivery were elevated. By contrast, circulating IGFBP-3 levels in both the mother and the fetus were lower in pre-eclampsia with IUGR than in nonpre-eclamptic pregnancy. However, there was no difference in serum IGFBP-1 and IGFBP-3 levels between pre-eclampsia without IUGR and nonpre-eclamptic pregnancy in both the mother and the fetus.
Conclusions In pre-eclampsia, elevated concentrations of circulating IGFBP-1 and decreased serum IGFBP-3 levels were observed in both the mother and the fetus. However, these changes may simply reflect low birthweight in pre-eclampsia.     

Oral 17beta-estradiol and sequential progesterone in menopause: effects on insulin-like growth factors and their binding proteins.

OBJECTIVE: We evaluated the acute effects of low-dose oral estradiol and sequential progesterone on the insulin-like growth factor (IGF)/growth hormone (GH) axis, IGF-binding proteins (IGFBPs) 1 and 3, and plasma levels of sex hormone-binding globulin (SHBG) in postmenopausal subjects. STUDY DESIGN: Thirty healthy normal-weight women (mean age: 54.2 +/- 5.7 years) spontaneously postmenopausal for at least 6 months were enrolled. None had used hormone replacement therapy (HRT). Appropriate investigations excluded renal, glucose, lipid and coagulation abnormalities. Breast X-ray and endometrial ultrasound examinations excluded organic pathologies. They received oral cyclical HRT for 1 year, based on the administration of oral estradiol (1 mg/day) for 28 consecutive days plus progesterone (200 mg/day) from day 15 to day 28; out of the whole group, 15 subjects received progesterone orally (group A), while in 15 progesterone was administered transvaginally (group B). On the day before treatment (T0), on day 14 (T14) and on day 28 (T28) of the first cycle, plasma levels of estradiol, progesterone, SHBG, GH, IGF-I and -II, IGFBP-1 and -3, insulin and C-peptide were assayed in all patients. The same parameters were evaluated at T14 and T28 during the 12th month of treatment. RESULTS: At T14, we observed significant increases in the levels of estradiol (from 20 +/- 16 to 115 +/- 71 pg/ml, p < 0.001), SHBG (from 132 +/- 42 to 182 +/- 55 nmol/l, p < 0.001) and IGFBP-1 (from 92 +/- 57 to 127 +/- 87 ng/ml, p < 0.004), while the level of IGF-I decreased (from 197 +/- 138 to 129 +/- 85 ng/ml, p < 0.003). At T28, progesterone levels were significantly higher in the women receiving it orally than transvaginally (8.4 +/- 6.1 vs. 3.7 +/- 3.2 ng/ml, p < 0.025). However, while oral progesterone did not affect the estrogen-induced variations, transvaginal progesterone abrogated the increase in the levels of IGFBP-1. The levels of IGF-II, IGFBP-3, GH, glucose, C-peptide and insulin did not change at any time. At 1 year, the values maintained the same trends. The estrogen-induced variations of SHBG were correlated directly with those of estradiol (r = 0.48) and inversely with those of IGF-I (r = -0.424). CONCLUSIONS: Low-dose oral estradiol reduces plasma levels of IGF-I and increases IGFBP-1 and SHBG concentrations, while GH is unchanged. These effects, significant and immediate, lead us to hypothesize a direct action of estradiol on hepatocytes.     

Effect of naloxone on plasma insulin, insulin-like growth factor I, and its binding protein 1 in patients with polycystic ovarian disease.

Insulin and insulin-like growth factors (IGFs) stimulate ovarian steroidogenesis, and hyperinsulinemia is often accompanied by hyperandrogenemia in women with polycystic ovarian disease (PCOD). Because opioid peptides are involved in the regulation of insulin secretion, we studied the effect of naloxone-induced opiate receptor blockade on the circulating levels of insulin, IGF-I, and IGF binding protein 1 (IGFBP-1) in 13 nonobese and 7 obese PCOD patients and in 6 healthy subjects. In obese PCOD patients, the mean basal insulin concentration was significantly higher and the IGFBP-1 concentration lower than in nonobese PCOD patients. Plasma IGF-I levels were elevated both in obese and nonobese PCOD patients. After an intravenous bolus of 10 mg naloxone, no significant changes were found in the circulating insulin or IGF-I levels, whereas IGFBP-1 levels decreased in nonobese PCOD patients and remained low in obese PCOD patients. No significant decrease was found in healthy subjects. These results suggest that, in addition to insulin, endogenous opioids are involved in the regulation of serum IGFBP-1 level.     

The pregnancy-associated plasma protein A and insulin-like growth factor system in response to cigarette smoking

Objective: Maternal smoking during pregnancy is associated with a reduction in birth size but the mechanism by which this occurs still remains unclear. The purpose of this study was to evaluate the effect of tobacco smoking on concentrations of pregnancy-associated plasma protein A (PAPP-A), insulin-like growth factor I (IGF-I), II (IGF-II) and binding proteins BP-3 and BP-4 in pregnant women and correlations between these parameters. Methods: Sixty healthy pregnant women were divided into smoking and tobacco-abstinent group according to results of serum cotinine concentration. The current smokers were defined as those who had smoked five or more cigarettes per day during pregnancy. Results: The mean serum concentrations of PAPP-A, IGF-I and IGF–II were significantly lower in smoking than in non-smoking pregnant women (p < 0.01). The level of PAPP-A correlated positively with the IGF-II concentration in both studied group (non-smoking: r = 0.54; p < 0.001; smoking: r = 0.40; p < 0.05). In tobacco-abstinent group negative correlation between IGF-II and IGFBP-4 concentrations was found (r = ?0.35; p < 0.05). Conclusion: Tobacco smoking during pregnancy decreases the pregnancy-associated plasma protein A and insulin growth factors I and II levels. The correlation between PAPP-A and IGF-II may suggest function of this protein as a protease and regulator in the IGF system.     

Effects of conjugated equine estrogen vs. raloxifene on serum insulin-like growth factor-i and insulin-like growth factor binding protein-3: a 2-year, double-blind, placebo-controlled study

OBJECTIVE: To assess and compare the effect of conjugated estrogen and of the selective estrogen receptor modulator raloxifene on serum levels of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) and on the IGF-I/IGFBP-3 ratio. DESIGN: A 2-year randomized, double-blind, placebo-controlled study. SETTING: Endocrinology outpatient department. PATIENT(S): Fifty-six postmenopausal, hysterectomized women. INTERVENTION(S): Women received raloxifene hydrochloride in doses of 60 mg/day (n = 15) or 150 mg/day (n = 13), conjugated equine estrogen (CEE) in doses of 0.625 mg/day (n = 15), or a placebo (n = 13) over the course of 2 years. MAIN OUTCOME MEASURE(S): At baseline and after 6, 12, and 24 months of treatment, serum levels of IGF-I, IGFBP-3, and insulin were measured, and an IGF-I/IFGBP-3 ratio was calculated. RESULT(S): Both raloxifene and CEE decreased serum IGF-I concentration. In contrast to CEE, which had no effect, both raloxifene doses of 60 and 150 mg/day significantly increased serum IGFBP-3 during the 2 years. Compared with placebo, the decrease in IGF-I/IGFBP-3 ratio was -32.5% (95% CI: -20.1; -44.8%) for CEE; -16.4% (95% CI: -3.6; -29.2%) for raloxifene at 150 mg/day; and -15.4% (95% CI: -1.0; -29.8%) for raloxifene at 60 mg/day. No effect of CEE or raloxifene was found on insulin concentration at any time point. CONCLUSION(S): Long-term use of both CEE and raloxifene decreases serum IGF-I and the IGF-I/IGFBP-3 ratio, but, unlike CEE, raloxifene produced a significant yet small increase in IGFBP-3.     

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