Regulation of insulin-like growth factor-I and insulin-like growth factor binding protein-1 concentrations in preterm fetuses

OBJECTIVE: Our purpose was to evaluate which factors regulate insulin-like growth factor-I and insulin-like growth factor binding protein-1 concentrations in preterm fetuses. STUDY DESIGN: We studied 76 singleton births between 25 and 36 weeks of gestation. Forty-nine pregnancies were complicated by hypertensive disease; 24 pregnancies were complicated by preterm labor or preterm rupture of membranes; and antenatal glucocorticoids were given in 49 pregnancies. Pathology reports showed infarct(s) or hematoma(s) in 31 of 69 placentas. We recorded blood gas values in umbilical artery and vein and measured glucose, C-peptide, and insulin-like growth factor-I and insulin-like growth factor binding protein-1 concentrations in umbilical vein. RESULTS: Birth weight correlated with umbilical vein insulin-like growth factor-I (r = 0.68, P <.0001) and inversely with insulin-like growth factor binding protein-1 (r = -0.26, P =.02). Babies with birth weight of 25th percentile. Two-factor analysis of variance showed that umbilical vein insulin-like growth factor-I was determined by gestational age (P =.0004) and birth weight percentile (P <.0001), whereas insulin-like growth factor binding protein-1 was not affected by gestational age. Umbilical vein C-peptide was highly correlated with insulin-like growth factor binding protein-1 (r = -0.55, P <.0001), but not insulin-like growth factor-I, levels. Blood gas values in umbilical artery and vein, particularly umbilical artery PO (2), were correlated with umbilical vein insulin-like growth factor-I and insulin-like growth factor binding protein-1 (r = 0.51 and -0.48, respectively; P <.0001); changes in insulin-like growth factor-I and insulin-like growth factor binding protein-1 occurred at umbilical artery PO (2) <14.8 mm Hg. Multiple regression analysis showed that umbilical vein insulin-like growth factor-I was predicted by umbilical artery PO (2), gestational age, and the presence of placental infarcts/hematomas (R (2) of model = 0.58, P <.0001), and umbilical vein insulin-like growth factor binding protein-1 by umbilical vein C-peptide, umbilical artery PO (2), and placental infarcts/hematomas (R (2) = 0.49, P <.0001). CONCLUSION: In the preterm fetus, circulating insulin-like growth factor-I is related to gestational age and the in utero growth potential, whereas insulin-like growth factor binding protein-1 is related only to the in utero growth potential. The PO (2) is a robust determinant of both insulin-like growth factor-I and insulin-like growth factor binding protein-1 levels; hypoxia may restrain fetal growth through its effects on the insulin-like growth factor/insulin-like growth factor binding protein axis. Insulin is a powerful determinant of insulin-like growth factor binding protein-1, but not insulin-like growth factor-I, concentrations in the preterm fetus.     

Transforming growth factor-beta1 in fetal serum correlates with insulin-like growth factor-I and fetal growth

OBJECTIVE: To estimate whether transforming growth factor-beta1 in fetal serum obtained by umbilical cord sampling at delivery is correlated with fetal growth. We also estimated whether transforming growth factor-beta1 is correlated with insulin-like growth factor-I and insulin-like growth factor binding protein-1, which have been shown to correlate with fetal growth. METHODS: The active form of transforming growth factor-beta1 was analyzed in serum from cord blood from 68 fetuses by the enzyme-linked immunosorbent assay technique. Of the 68 pregnant women, 12 had preeclampsia, 14 had preeclampsia and intrauterine growth restriction, 15 had intrauterine growth restriction alone, and seven had fetuses that were large for gestational age (LGA). Twenty pregnancies with fetuses appropriate for gestational age (AGA) served as controls. RESULTS: Transforming growth factor-beta1 concentrations were significantly correlated with birth weight. The average transforming growth factor-beta1 concentration in the following groups were: intrauterine growth restriction, 22.4 +/- 2.7 microg/L; intrauterine growth restriction plus preeclampsia, 22.9 +/- 2.0 microg/L; preeclampsia without intrauterine growth restriction, 28.8 +/- 2.1 microg/L; LGA, 30.3 +/- 4.3 microg/L; and AGA, 36.8 +/- 2.0 microg/L. Transforming growth factor-beta1 levels were significantly lower in pregnancies complicated by intrauterine growth restriction and showed a positive correlation with birth weight (r = 0.48, P <.001). Furthermore, there was a positive correlation between insulin-like growth factor-I levels and birth weight (r = 0.36, P <.01) and a negative correlation between insulin-like growth factor binding protein-1 and birth weight (r = -0.32, P <.01). There was also a correlation between transforming growth factor-beta1 and insulin-like growth factor-I (r = 0.29, P <.05) and between transforming growth factor-beta1 and insulin-like growth factor binding protein-1 (r = -0.25, P <.05). CONCLUSION: Transforming growth factor-beta1 might be related to fetal growth in pregnancy. The results also support previous data showing that insulin-like growth factor-I and insulin-like growth factor binding protein-1 are related to fetal growth.     

Progestins abrogate estrogen-induced changes in the insulin-like growth factor axis

OBJECTIVE: We sought to investigate the effect of oral progestins on estrogen-mediated changes in the insulin-like growth factor axis in the peripheral circulation. STUDY DESIGN: Oral conjugated equine estrogen alone or in combination with medroxyprogesterone acetate, desogestrel, or norethindrone was given in a randomized triple-crossover fashion to 10 healthy postmenopausal women, and the effects on the insulin-like growth factor axis were determined. RESULTS: Baseline circulating insulin-like growth factor I levels were significantly reduced by conjugated equine estrogen (359 +/- 54 vs 225 +/- 44 ng/mL; P =.0001). This effect was reversed by progestins (medroxyprogesterone acetate, 254 +/- 44 ng/mL; desogestrel, 266 +/- 50 ng/mL; norethindrone, 286 +/- 48 ng/mL; F = 12.2; P =.0015). Free insulin-like growth factor I was reduced by conjugated equine estrogen (1.00 +/- 0.15 ng/mL vs 2.10 +/- 0.39 ng/mL; P =.004), but addition of progestogens had no further effect. Insulin-like growth factor II and insulin levels were unaffected by conjugated equine estrogen or progestins. Plasma insulin-like growth factor binding protein 1 concentration increased significantly from baseline with conjugated equine estrogen alone (44.1 +/- 6.0 vs 154 +/- 30 microg/L; P =.003). This rise was opposed by progestins of increasing androgenicity (medroxyprogesterone acetate, 130 +/- 26 microg/L; desogestrel, 100 +/- 16 microg/L; norethindrone, 78.0 +/- 12 microg/L; F = 12.5; P =.0015). Insulin-like growth factor binding protein 3 levels fell with conjugated equine estrogen, and this was reversed by progestins (conjugated equine estrogen, 2.17 +/- 0.13 mg/L; vs norethindrone and conjugated equine estrogen, 2.41 +/- 0.12 mg/L; F = 7.6; P =.01). Insulin-like growth factor binding protein 4 levels increased with conjugated equine estrogen with or without progestins, whereas insulin-like growth factor binding protein 2 levels were unchanged. CONCLUSIONS: Coadministration of androgenic progestins abrogates estrogen-related changes in circulating insulin-like growth factor I, insulin-like growth factor binding protein 1, and insulin-like growth factor binding protein 3. Such hormone replacement therapy-induced changes may have significant consequences for the development of cardiovascular disease and osteoporosis and implications for the use of insulin-like growth factor I in monitoring growth hormone replacement.     

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.     

Insulin-like Growth Factor Binding Protein-3 in the Detection of Fetal Down Syndrome Pregnancies

Objective: To study the usefulness of maternal serum insulin-like growth factor binding protein-3, a potential cell growth inhibitor, in second trimester prenatal screening for fetal Down syndrome.Methods: Three hundred and forty-two samples from normal pregnancies and nine fetal Down syndrome pregnancies were analyzed for insulin-like growth factor binding protein-3 levels by radioimmunoassay. Data were converted to multiples of median (MoM) and analyzed statistically to compare the differences between control and Down syndrome pregnancies.Results: The mean insulin-like growth factor binding protein-3 MoM of Down syndrome–affected pregnancies (1.09) was significantly higher than that of the normal pregnancies (1.00) (P < .01). Insulin-like growth factor binding protein-3, in combination with maternal serum alpha-fetoprotein (MSAFP), hCG, and maternal age, detected 89% of Down syndrome pregnancies at a screen positive rate of 2.1%. This compares favorably to the standard combination of MSAFP, hCG, and unconjugated estriol (E3), which had a 66.7% Down syndrome detection rate and a 4.1% screen positive rate in our study samples.Conclusion: This retrospective analysis suggested that the inclusion of insulin-like growth factor binding protein-3 into the triple screen program to replace unconjugated E3 might enhance the detection rate of fetal Down syndrome pregnancies. These data need to be confirmed by a larger prospective study.     

Relationship of insulin-like growth factor-I and insulin-like growth factor binding proteins in umbilical cord plasma to preeclampsia and infant birth weight.

OBJECTIVE: To determine whether preeclampsia influences insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-1 (IGFBP-1), and insulin-like growth factor binding protein-3 (IGFBP-3), independent of its effect on birth weight. METHODS: Cord blood was collected in 12,804 consecutive deliveries. We identified 258 preeclamptic pregnancies that were subclassified as mild or severe and early or late. For comparison, 609 control pregnancies were selected. Fetal growth was expressed as the ratio between observed and expected birth weight, with adjustment for gestational age at birth. IGF-I, IGFBP-1, and IGFBP-3 were measured in umbilical plasma. The contribution of preeclampsia and birth weight to each measured factor was assessed by multiple linear regression analyses. RESULTS: Between mild preeclampsia and controls, there were no differences in IGF-I, IGFBP-1, and IGFBP-3. In severe and early onset preeclampsia, umbilical cord plasma IGF-I was approximately 50% lower, and IGFBP-1 was more than twice as high as in controls (both P <.01). At each birth weight level, IGF-I was lower and IGFBP-1 was higher in severe or early preeclampsia than among controls of similar weight. Birth weight and preeclampsia were, independent of each other, associated with IGF-I, whereas birth weight, but not preeclampsia, was associated with IGFBP-1, after adjustment for gestational age. CONCLUSION: Fetal growth restriction caused by severe or early preeclampsia is associated with lower umbilical levels of IGF-I than low birth weight caused by other conditions. Preeclampsia may contribute to the observed IGF-I reduction, either as part of the underlying causes of preeclampsia, or as a consequence of the disease.     

Serum insulin-like growth factor binding protein-1 at 16 weeks and subsequent preeclampsia

OBJECTIVE: To determine whether serum concentrations of insulin-like growth factor-binding protein-1 (IGFBP-1), a major decidual protein, at 16 weeks' gestation differ between women who later develop pregnancy-related hypertension and normotensive women. METHODS: Concentrations of IGFBP-1 were measured using immunoenzymometric assay in serum samples collected for alpha-fetoprotein (AFP) and free beta subunit of hCG (free beta-hCG) determinations in a Down syndrome screening program at 16 weeks' gestation in a population-based cohort of 1049 nulliparous women. After exclusion of subjects with multiple pregnancies, insulin-dependent diabetes, major fetal malformations, and incomplete data, 917 subjects remained eligible. RESULTS: The mean levels (+/- standard deviation) of IGFBP-1 were significantly lower in 34 women who later developed preeclampsia (73 +/- 43 microg/L, P < .01) and in 80 women with White A diabetes (84.7 +/- 53 microg/L, P < .01) compared with controls (103 +/- 58 microg/L). In seven women with White A diabetes and subsequent preeclampsia IGFBP-1 levels were especially low (41 +/- 34 microg/L). The concentrations of AFP and free beta-hCG in the subgroups with hypertensive disorders were not significantly different from those of normotensive women. CONCLUSION: Decreased IGFBP-1 levels at 16 weeks' gestation in women who develop preeclampsia might indicate impaired decidual function. Hyperinsulinemia, a known risk factor for preeclampsia, might contribute to decreased concentrations of serum IGFBP-1. However, due to low sensitivity, assay of serum IGFBP-1 was not clinically valuable for predicting preeclampsia.     

Maternal serum insulin-like growth factor binding protein-1 in pregnancy at high altitude

OBJECTIVE: To investigate the effect of environmental hypoxia at 4300-m altitude on the maternal serum concentration of insulin-like growth factor binding protein-1 (IGFBP-1). METHODS: We conducted a cross-sectional study of 108 pregnant women in Peru, 62 from high altitude (4300 m, 14100 ft) and 46 from sea level at 14-42 weeks' gestation. For comparison, 20 healthy nonpregnant women (ten from high altitude and ten from sea level) were also examined. Total and nonphosphorylated IGFBP-1 were measured in maternal serum. RESULTS: Both total and nonphosphorylated IGFBP-1 were higher at high altitude than at sea level in the pregnant groups (ratio = 1.28, P =.008, and ratio = 1.45, P =.003, respectively), and there was significant interaction between high altitude and sea level (P =.037 and P =.043, respectively). The threshold model showed that the difference became significant from 25 weeks' gestation onwards. CONCLUSION: Before 25 weeks of pregnancy, there was no significant difference in IGFBP-1 between women living at high or low altitude, suggesting that the increased IGFBP-1 at high altitude is unlikely to be related to inadequate trophoblast invasion resulting in placental hypoxia. In the second half of pregnancy, the maternal and fetal demands increase dramatically, and low atmospheric oxygen with resulting maternal systemic hypoxemic hypoxia may cause placental hypoxia. This stimulates increased production of IGFBP-1, which in turn restricts the insulin-like growth factor-mediated fetal growth as an adaptive mechanism to prevent worsening of the fetoplacental hypoxia.     

Insulin,insulin-like growth factor-1, and insulin resistance in women with pregnancy-induced hypertension

OBJECTIVE: The purpose of this study was to assess insulin, insulin sensitivity, and insulin-like growth factor-I in women with preeclampsia and gestational hypertension. STUDY DESIGN: Insulin resistance was measured with the short insulin-tolerance test in 20 women with preeclampsia, in 18 women with gestational hypertension, and in 20 normotensive control subjects. Sex hormone binding globulin, insulin-like growth factor-I, glucose, fructosamine, glycosylated hemoglobin, insulin, C-peptide, and lipids were measured in the fasting state. RESULTS: Women with gestational hypertension had a significant lower insulin sensitivity index (0.13 +/- 0.1) and a higher level of insulin-like growth factor-I (333.71 +/- 107.6 ng/mL) than women in the control group (0.21 +/- 0.1 [P <.05]; 218.11 +/- 82.3 ng/mL [P <.01]) and women with preeclampsia (0.21 +/- 0.12 [P <.05]; 234.78 +/- 92.76 ng/mL [P <.01]). There were no significant correlations between insulin sensitivity index and insulin-like growth factor-I. CONCLUSION: Insulin resistance is present in women with gestational hypertension but not in women with preeclampsia and did not correlate with insulin-like growth factor-I.     

Secretion of prolactin and insulin-like growth factor I by decidual explant cultures from pregnancies complicated by intrauterine growth retardation.

OBJECTIVES: Prolactin and insulin-like growth factor I secretion elsewhere in the uterus have been shown to decrease when tissue-specific growth is limited. We investigated their secretion by decidual explant cultures from pregnancies complicated by fetal intrauterine growth retardation. STUDY DESIGN: Explant cultures from 13 pregnancies complicated by intrauterine growth retardation and 12 control pregnancies were established in minimal essential medium and media was harvested after 24 hours of culture. Prolactin and insulin-like growth factor I concentrations were determined by radioimmunoassay. Total protein in the media was also measured. Data were analyzed by analyses of variance and linear regression. RESULTS: Decidual prolactin secretion in the pregnancies with intrauterine growth retardation was reduced to 109 +/- 31 ng/100 mg tissue per 24 hours compared with 254 +/- 51 ng in the controls (p = 0.01). Insulin-like growth factor I secretion was reduced to 1.9 +/- 0.6 ng/100 mg tissue per 24 hours from 7.1 +/- 0.9 ng/100 mg in the controls (p < 0.0001). Total protein secretion did not differ between the two groups. Decidual prolactin and insulin-like growth factor I secretion had a highly significant positive correlation (r = 0.71, p = 0.0001). CONCLUSIONS: Our data show that two protein hormones secreted by the maternal decidua are dramatically reduced in intrauterine growth retardation and warrant further investigation into their roles in the intrauterine environment.     

Immunohistochemical staining of IGF-I,IGF-binding proteins-1 and -3, and transforming growth factor beta-3 in the umbilical cords of preeclamptic patients

BACKGROUND: To detect the immunoreactivity of insulin-like growth factor-I, insulin-like growth factor-binding proteins-1 and -3 and transforming growth factor beta-3 in the umbilical cords of normal and preeclamptic patients. METHODS: Umbilical cords were obtained from 15 normal and 15 preeclamptic patients. Immunoreactivities were determined using either indirect immunofluorescence or immunoperoxidase techniques on formalin-fixed, paraffin-embedded sections. Staining intensity was graded by a semiquantitative scoring method. The results were compared by Mann-Whitney U-test. RESULTS: The umbilical cords were thinner and the vessels were hypoplastic in the preeclamptic group. Moderate staining intensity for insulin-like growth factor-I, insulin-like growth factor binding protein-1 and -3 and transforming growth factor-beta 3 was observed in normal patients. The preeclamptic group had mild and strong intensities for insulin-like growth factor-I and insulin-like growth factor binding protein-1, respectively, and intensity for insulin-like growth factor binding protein-3 did not change, but diffuse and increased intensity was observed for transforming growth factor-beta 3. CONCLUSION: Changes in the intensity of insulin-like growth factor-I and its major binding protein and the transformation of growth factor-beta 3 may play a role in the pathogenesis of preeclampsia by altering the structure and responsiveness of the umbilical cord.     

Diabetic pregnancy associated with increased epidermal growth factor in cord serum at term

OBJECTIVE: Epidermal growth factor is a ubiquitous mitogen that also possesses insulin-like properties. Fetal mal-growth is associated with altered epidermal growth factor levels. Maternal diabetes is frequently complicated by macrosomia, but the effect of maternal diabetes on fetal epidermal growth factor levels is not known. We studied cord serum epidermal growth factor concentrations in pregnancies complicated by diabetes and in normal pregnancies. METHODS: Cord serum epidermal growth factor concentrations were measured at birth by a sandwich-type time-resolved immunofluorometric assay in 63 pregnancies complicated by insulin-dependent diabetes mellitus, in 25 pregnancies complicated by insulin-treated gestational diabetes, and in 56 normal pregnancies. RESULTS: Cord serum epidermal growth factor correlated positively with the duration of pregnancy in diabetic and normal pregnancies. In a subgroup of women at similar gestational ages (38-39 weeks), cord serum epidermal growth factor concentrations were higher in pregnancies complicated by insulin-dependent diabetes mellitus (962 +/- 211 ng/L, P =.047; n = 9) and in pregnancies complicated by gestational diabetes (1133 +/- 115 ng/L, P =.001; n = 9) than in controls (564 +/- 75 ng/L; n = 22). In multiple regression analysis, only umbilical artery hemoglobin in diabetic pregnancies and vaginal delivery in normal pregnancies were associated with cord serum epidermal growth factor. CONCLUSION: Epidermal growth factor concentrations are higher than normal in fetuses of diabetic mothers at term. Pregnancy complications, such as hypertensive disorders, fetal hypoxia and fetal malgrowth, may not explain the rise in epidermal growth factor levels. We hypothesize that the rise in epidermal growth factor levels is a metabolic response of the fetoplacental unit to diabetes-related hyperglycemia. LEVEL OF EVIDENCE: III     

Oral contraceptives increase insulin-like growth factor binding protein-1 concentration in women with polycystic ovarian disease.

Insulin-like growth factor-I (IGF-I) stimulates ovarian androgen production. Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits IGF actions in vitro. OBJECTIVE: To investigate the effect of oral contraceptive (OC) pills, given for 3 months, on serum gonadotropin, androgen, IGF-I, and IGFBP-1 concentrations, and glucose tolerance in seven women with polycystic ovarian disease (PCOD) and in five healthy control subjects. PATIENTS: Seven women with PCOD and five healthy control subjects. INTERVENTIONS: An oral glucose tolerance test (OGTT) was performed before and after treatment with OC. RESULTS: After treatment with OC, serum luteinizing hormone, androstenedione, and free testosterone levels decreased, and sex hormone-binding globulin concentration increased in the women with PCOD as well as in the control subjects. The cumulative response of serum insulin to OGTT was larger in the women with PCOD than in the control subjects both before and after treatment. Serum IGF-I concentration, which was unchanged during OGTT, decreased from basal level of 326 +/- 70 micrograms/L to 199 +/- 28 micrograms/L after treatment with OC in the women with PCOD, whereas no change was found in the control subjects (from 235 +/- 11 micrograms/L to 226 +/- 11 micrograms/L). Treatment with OC caused an increase of the mean basal IGFBP-1 concentration from 24 +/- 7 micrograms/L to 73 +/- 14 micrograms/L in the women with PCOD. This increase was constant during the OGTT. In the control subjects, treatment with OC did not result in any significant change in IGFBP-1 concentrations (from 44 +/- 11 micrograms/L to 61 +/- 9 micrograms/L). CONCLUSION: The combination of decreased total IGF-I concentration and increased IGFBP-1 concentration induced by OC may decrease ovarian androgen production in PCOD.     

Increased insulin-like growth factor-I levels in women with polycystic ovary syndrome, and beneficial effects of metformin therapy.

We aimed to investigate whether metformin would reverse the endocrinopathy of polycystic ovary syndrome (PCOS), allowing resumption of cyclic ovulation and regular menses, and whether metformin causes any change in the serum concentration of insulin-like growth factor-I (IGF-I) in patients with PCOS. Fifty-eight women with PCOS participated in the study and received metformin at a dose of 850 mg three times a day (total 2550 mg) for 16 weeks. Serum concentrations of luteinizing hormone, follicle stimulating hormone, estradiol, free testosterone, total testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, fasting insulin, IGF-I, sex hormone binding globulin and insulin-like growth factor binding protein-1 (IGFBP-1) were evaluated before and after metformin treatment. Patients were divided into two groups as responders and non-responders according to the achievement of regular menstrual periods. The mean IGF-I levels decreased significantly on metformin therapy. After 16 weeks of metformin treatment, 55.17% of PCOS patients achieved regular menses. Only the change in serum levels of progesterone and IGF-I on metformin were statistically significant between responders and non-responders; metformin-induced decremental change in IGF-I levels were greater in responders. In conclusion, we observed that elevated IGF-I levels may have a crucial role in many consequences of PCOS in addition to hyperinsulinemia. By decreasing insulin and IGF-I levels, metformin therapy offers additional beneficial effects in resumption of regular menses. Thus, in PCOS patients with elevated levels of IGF-I, metformin may be considered as an appropriate agent to be used for the regulation of menstrual cycles.     

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     

Fasting serum growth hormone and insulin-like growth factor-I and -II concentrations in women with leiomyomata uteri treated with leuprolide acetate or placebo

Eighteen patients with leiomyomata uteri were randomized to receive either leuprolide acetate depot (n = 9) 3.75 mg intramuscularly (IM) or placebo (n = 9) IM every 4 weeks for four injections. Leuprolide acetate treated patients demonstrated a reduction in mean uterine volume of 34% and a decrease in serum estradiol (E2) concentrations from 120 +/- 21 pg/mL (mean +/- standard error) to 16 +/- 9 pg/mL. Leuprolide acetate treated patients also demonstrated significant decreases in serum growth hormone (GH) (3.0 +/- 0.4 ng/mL versus 1.4 +/- 0.4 ng/mL) and insulin-like growth factor-I (IGF-I) concentrations (3.3 +/- 0.4 U/mL versus 1.3 +/- 0.2 U/mL) over the 12 week treatment period. Serum IGF-II levels did not change. Mean uterine volume and serum E2, GH, IGF-I, and IGF-II concentrations did not change in placebo-treated patients. These data suggest that hypoestrogenism is associated with decreases in circulating GH and IGF-I.     

The relationship among serum insulin-like growth factor-I, insulin-like growth factor-I gene polymorphism, and bone mineral density in postmenopausal women in Korea

OBJECTIVE: The objective of this study was to test the hypothesis that the cytosine-adenine polymorphism in the insulin-like growth factor-I gene is associated with serum insulin-like growth factor-I levels and bone mineral density. STUDY DESIGN: The insulin-like growth factor-I cytosine-adenine polymorphism was analyzed in 300 postmenopausal Korean women. Serum insulin-like growth factor-I, bone alkaline phosphatase, and carboxy-terminal cross-linking telopeptide of type I collagen were measured by immunoradiometric assay and enzyme-linked immunosorbent assay. Bone mineral density at the lumbar spine and proximal femur was determined by dual energy radiograph absorptiometry. RESULTS: Serum insulin-like growth factor-I and bone mineral density levels in women who were homozygous for a 194-base pair allele were significantly higher than those levels in the 194-base pair heterozygotes or women who did not possess the 194-base pair allele. A significantly decreased prevalence of the 194/194 genotype was observed in the combined group of women with osteopenia and osteoporosis, compared with normal women. No correlation between insulin-like growth factor-I genotypes and bone turnover markers was found. CONCLUSION: The insulin-like growth factor-I gene cytosine-adenine polymorphism relates with circulating insulin-like growth factor-I levels and bone mineral density at the lumbar spine and proximal femur.     

Maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks in trisomy 21 and trisomy 18 pregnancies

Objective

To investigate the possible value of maternal serum concentration of insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1) and IGFBP-3 in first-trimester screening for fetal aneuploidies.

Study design

Maternal serum concentrations of IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks of gestation were measured and compared in 30 trisomy 21, 30 trisomy 18 and 120 euploid pregnancies.

Results

The median multiple of the normal median (MoM) values of maternal serum IGF-I, IGFBP-1 and IGFBP-3 in trisomy 21, trisomy 18 and euploid pregnancies were not significantly different (IGF-I: 1.10, 1.14 and 1.0 MoM, respectively; IGFBP-1: 1.10, 1.01 and 1.0 MoM; IGFBP-3: 0.90, 1.16 and 0.98 MoM).

Conclusion

Measurement of maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks of gestation is unlikely to be useful in screening for trisomies 21 and 18.     

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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