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1.
Giudice L.C.; Irwin J.C.; Dsupin B.A.; Pannier E.M.; Jin I.H.; Vu T.H.; Hoffman A.R. 《Human reproduction (Oxford, England)》1993,8(11):1796-1806
Oestradiol is important in the growth of uterine leiomyomataand may act primarily or secondarily through mediators suchas growth factors, including the insulin-like growth factors(IGF-I and IGF-II), mitogenic peptides. IGF binding proteins(IGFBPs) modulate IGF actions at their target cells. The objectiveof this study was to examine the possible steroid dependenceof IGF, IGFBP and IGF receptor gene expression and IGFBP synthesisin uterine leiomyomata, using tissues from women cycling normallyand made hypo-oestrogenic by a gonadotrophin-releasing hormoneagonist (GnRHa). Using a solution hybridization ribonucleaseprotection assay, anti-sense RNA probes for IGF-I, IGF-II and-actin (control) were hybridized with total RNA isolated fromleiomyomata exposed in vivo to a range of serum oestradiol (<40240pg/ml) and progesterone (010 ng/ml) concentrations. IGF-Igene expression was most abundant in leiomyomata obtained duringthe late proliferative phase of the cycle and was undetectablein leiomyomata from hypo-oestrogenic patients. IGF-II gene expressionwas not dependent on endogenous steroid concentrations or cyclestage. IGFBP gene expression was investigated by Northern blotting.The order of relative abundance of IGFBP mRNAs was IGFBP-4 >> > IGFBP-3 > > IGFBP-5 > IGFBP-2 and was notdependent on the in-vivo oestrogen status. Type I and type IIIGF receptor gene expression was investigated by polymerasechain reaction using gene-specific primers. Type I and typeII IGF receptor mRNAs were detected in leiomyomata and werenot dependent on cycle stage or in-vivo oestrogen status. Explantcultures of leiomyomata and myometrium synthesized IGFBP-3 (mol.wt = 3843 kDa), IGFBP-4, and binding proteins of mol.wt = 34 and 31 kDa. Identification of IGFBP-2 was inconclusive,and IGFBP-1 was not detected. These data support the hypothesisthat IGF-I, but not IGF-II, may be a mediator of oestradiolaction in the growth of uterine leiomyomata, and that IGFBPsmay further modulate, by an autocrine or paracrine mechanism,IGF-I action in this tissue. 相似文献
2.
Prenatal exposure to excess testosterone modifies the developmental trajectory of the insulin-like growth factor system in female sheep 总被引:2,自引:0,他引:2
Erica J. Crespi Teresa L. Steckler Puliyur S. MohanKumar Vasantha Padmanabhan 《The Journal of physiology》2006,572(1):119-130
Experimental elevation of maternal testosterone (T) from 30 to 90 days of gestation leads to intrauterine growth retardation (IUGR) and increased prepubertal growth rate in female lambs. This study tested the hypothesis that prenatal T treatment during mid-gestation alters the trajectory of the fetal insulin-like growth factor (IGF)–insulin-like growth factor binding protein (IGFBP) system to promote IUGR and subsequent postnatal catch-up growth in female lambs. Plasma IGF-I and IGFBPs were measured by radioimmunoassay and Western ligand blot, respectively, on 65, 90 and 140 days (d) of gestation, at birth, ∼5 months (prepubertal, the catch-up growth period), and ∼9.5 months (postpubertal). Northern blot analysis was used to measure hepatic mRNA content of IGF system components during fetal stages. At fetal 65 d, plasma protein and hepatic mRNA content of IGFBP-1, an inhibitor of IGF bioactivity, was elevated in prenatal T-treated fetuses although body weight did not differ. There was a transient increase in plasma IGF-I and IGFBP-3 concentrations at fetal 90 d in prenatal T-treated fetuses. Hepatic IGF-I mRNA and plasma IGFBP-3 content were reduced by 140 d when body weight was reduced in prenatal T-treated fetuses. Plasma IGFBP-2 content was significantly reduced in prenatal T-treated newborns, but by 4 months these females had significantly higher circulating IGF-I and IGFBP-3 concentrations and faster growth rates than control females. After puberty, plasma IGF-I remained elevated in prenatal T-treated females. These findings provide evidence that prenatal T excess programmes the developmental trajectory of the IGF/IGFBP system in female sheep to reduce IGF bioavailability during IUGR and increase IGF bioavailability during prepubertal catch-up growth. 相似文献
3.
Bernardi F; Petraglia F; Seppala M; Spinetti A; Bertolini S; Ferdeghini M; Genazzani AR 《Human reproduction (Oxford, England)》1998,13(2):279-284
The altered function of the somatotropic axis observed in perimenopause may
underlie the changes in body weight and fat distribution. The aim of the
present study was to evaluate, in pre-menopausal and post- menopausal women
with body mass index (BMI) > or = or <25, the basal plasma levels of
growth hormone (GH), insulin-like growth factor (IGF)- I and -II, IGF
binding protein (IGFBP)-1 and -3, and the response of GH and IGFBP-1 and -3
to GH releasing hormone (GHRH) and GHRH plus arginine tests. GH and IGF-I
basal concentrations were significantly higher in pre-menopausal than in
post-menopausal women, while IGF-II, IGFBP-1 and IGFBP-3 concentrations did
not vary significantly. IGFBP-1, but not IGFBP-3, concentrations were
higher in lean than in obese patients. Insulin concentrations were
significantly higher in obese patients, while no differences were observed
between pre-menopausal and post-menopausal women. In all subjects, GH
concentrations increased significantly during GHRH test; pre-menopausal and
lean women showed a higher response compared to post-menopausal and obese
women. The GHRH plus arginine test stimulated GH response in all women,
irrespective of age and BMI. IGFBP-1 and -3 concentrations did not vary in
response to GHRH or GHRH plus arginine tests. The somatotropic axis
undergoes modifications in post-menopausal women, apparently not involving
IGFBP- 1 and -3. Arginine infusion restores the response of GH to GHRH, in
both post-menopausal and obese subjects. A somatostatinergic hyperactivity
at the climateric period may underlie the changes both in body weight and
somatotropic axis.
相似文献
4.
Homburg Roy; Orvieto Raoul; Bar-Hava Itai; Ben-Rafael Zion 《Human reproduction (Oxford, England)》1996,11(4):716-719
In order to determine which factors influence the large variationsin sensitivity to gonadotrophins witnessed in women with polycysticovary syndrome (PCOS), a prospective study was conducted ofthe correlation between basal clinical and endocrinologicalfeatures and gonadotrophin requirements of 20 women with clomiphene-resistantPCOS undergoing ovulation induction. Baseline evaluation ofserum concentrations of luteinizing hormone (LH), follicle stimulatinghormone (FSH), testosterone, fasting insulin, insulin-like growthfactor-1 (IGF-1), IGF binding protein-1 (IGFBP-1) and sex hormone-bindingglobulin (SHBG) were performed before administering gonadotrophin-releasinghormone agonist (GnRHa). Two weeks later, human menopausal gonadotrophin(HMG) was given in a standard individualized protocol accordingto ovarian response, until human chorionic gonadotrophin (HCG)was given. Serum concentrations of insulin, IGF-1, and IGFBP-1were unaffected by GnRHa. The BMI correlated positively withinsulin and inversely with IGFBP-1 serum concentrations andinsulin and IGFBP-1 were inversely correlated. The amount ofHMG required correlated positively with BMI and insulin concentrationsand inversely with IGFBP-1 in the whole group and these correlationswere maintained in the sub-group of lean women. No correlationwas observed between HMG requirements and IGF-1 or other hormones.Womenwith hyperinsulinaemia and low IGFBP-1 concentrations requiredsignificantly more HMG. Multiple regression analysis revealedthat insulin concentration is the most significant determinantof HMG requirement even when dissociated from BMI. We concludedthat requirement of HMG in PCOS is not merely determined byobesity but by a cardinal role of insulin concentrations which,when high, induce, hypothetically, a hyperandrogenic intrafollicularmilieu. 相似文献
5.
《Annals of human biology》2013,40(2):194-202
Background: Height and BMI are risk factors for several types of cancer and may be related to circulating concentrations of insulin-like growth factor-I (IGF-I), a peptide associated with increased cancer risk.Aim: To assess the associations between height, BMI and serum concentrations of IGF-I and IGF binding protein (IGFBP)-1, -2 and -3.Subjects and methods: This cross-sectional analysis included 1142 men and 3589 women aged 32–77 years from the multi-centre study, the European Prospective Investigation of Cancer and Nutrition (EPIC).Results: In men, there was a positive association between height and IGF-I; each 10 cm increment in height was associated with an increase in IGF-I concentrations of 4.3% (95% confidence interval (CI): 1.3–7.5%, p for trend = 0.005), but this association was not statistically significant for women (0.9%, 95% CI: ? 0.7 to 2.6%, p for trend = 0.264). In both men and women, the association between IGF-I and BMI was non-linear and those with a BMI of 26–27 kg/m2 had the highest IGF-I concentration. BMI was strongly inversely related to concentrations of IGFBP-1 and IGFBP-2 in men and in women (p for trend for all < 0.001).Conclusion: Height and BMI are associated with IGF-I and its binding proteins, which may be mechanisms through which body size contributes to increased risk of several cancers. 相似文献
6.
M Hamori W F Blum A T?r?k R Stehle E Waibel P Cledon M B Ranke 《Human reproduction (Oxford, England)》1991,6(3):313-318
Increasing evidence suggests that insulin-like growth factors I and II (IGF-I, IGF-II) have a regulatory role in animal granulosa cells. This study was undertaken to investigate the presence of IGF-I and IGF-II, as well as that of their binding proteins (BP), IGFBP-1 and IGFBP-3 in human serum and follicular fluid (FF). Preovulatory FF was obtained from 51 patients undergoing in-vitro fertilization. The IGFBP-1 level was found to be significantly higher (P less than 0.01) in FF than in serum, whereas IGF-I and IGFBP-3 values remained markedly lower (P less than 0.01) in FF. Serum IGF-II levels were slightly but not significantly elevated compared to values obtained in the FF of patients. A positive correlation (P less than 0.001) between individual serum and FF levels was observed only for IGF-I. When a group of poor responders was compared to patients with normal stimulation characteristics, no significant difference was found in either IGF or IGFBP levels in the FF. It is concluded that IGFBP-1 is produced locally, whereas the serum may possibly be the major source of IGF-I. No clear conclusions can be drawn regarding the source of FF IGF-II and IGFBP-3. Neither the absolute level nor the relationship of IGFs to their transport proteins could explain the poor response to ovarian stimulation. 相似文献
7.
The IGF/IGFBP system in CNS malignancy. 总被引:12,自引:0,他引:12
8.
Lai Ying Ming; Wang Hsin Shih; Lee Chyi Long; Lee Jing Der; Huang Hong Yuan; Chang Fu Hsing; Lee Jo Fang; Soong Yung Kuei 《Human reproduction (Oxford, England)》1996,11(6):1281-1286
Co-culturing embryos on helper cells can mimic the in-vivo environment,thereby enhancing embryo development in vitro. Insulin-likegrowth factors (IGF) and their binding proteins (IGFBP) alsoenhance embryo development To investigate the kinds of IGFBPproduced by various cell monolayers and the effects of IGFBP-3on mouse embryo co-culture systems, 2-cell ICR mouse embryoswere cultured in either human tubal fluid medium alone or inthe presence of Vero cells, human oviductal cells or endometrialcells. The helper cells were analysed immunohisto-chemicallyto investigate the types of IGFBP produced by various cell monolayers.The concentrations of IGF-I and IGFBP-3 in media obtained fromthe culture of embryos alone, cells alone or cells plus embryoswere determined by radioimmunoassays. On day 7, more blastocystshatched in the co-culture groups (73% in the Vero cell group,76% in the endometrial cell group and 74% in the oviductal cellgroup) than in the control group (43%) (P < 0.0001). Theresults of immunohistochemistry revealed that (i) all threecell groups produced a lot of IGFBP-1, -2 and -3, but only alittle of IGFBP-4 and -5; and (ii) IGFBP-1, -2 and -3 were presentin blastocysts in either the presence or absence of helper cells.The IGF-I secreted by cell monolayers or embryos was undetectable(detection limit 0.83 ug/1). The IGFBP-3 concentrations in mediaobtained from co-cultured embryos and cells were significantlyhigher than in media without embryos (median values in oviductalcell culture medium, 165 versus 127 µg/1, P = 0.04; medianvalues in endometrial cell culture medium, 277.5 versus 183.5µg/1, P = 0.0002; median values in Vero cell culture medium,219 versus 120 µg/1, P = 0.011). Although IGFBP-3 concentrationin the medium that contained embryos alone was undetectableby radioimmuno-assay (detection limit 1.1 µg/1), immunohistochemistrydemonstrated the presence of IGFBP-3 in the embryos. Co-culturein systems in which there was an increased production of IGFBP-3led to an improved development of mouse embryos. IGFBP can improvethe binding of IGF to cell surface receptors of target tissue,and thus enhance the effect of limited IGF concentrations inpromoting embryo development in a co-culture system. We concludethat Vero cells, human endometrial cells and oviductal cellsproduce IGFBP-1, -2, -3, -4 and -5. IGFBP-3 may play a rolein embryotrophic potential by either regulating the action ofIGF or directly enhancing embryo development 相似文献
9.
Choi YS Ku SY Jee BC Suh CS Choi YM Kim JG Moon SY Kim SH 《Human reproduction (Oxford, England)》2006,21(8):2015-2021
BACKGROUND: Insulin-like growth factors (IGF) and their binding proteins (IGFBP) play a major role in the autocrine and paracrine regulation of folliculogenesis. This is the first study that has compared follicular fluid (FF) IGF-I, IGF-II, IGFBP-3, IGFBP-4 and pregnancy-associated plasma protein (PAPP)-A concentrations, and their ratios, to investigate whether there was any difference in the intrafollicular microenvironment between the GnRH agonist (GnRHa) and antagonist (GnRHant) protocols for controlled ovarian stimulation (COS). METHODS: A total of 68 IVF cycles were included in this study; two groups were studied: GnRHa long protocol group (n = 36) and the flexible GnRHant multiple-dose protocol group (n = 32). FF was obtained from dominant follicles during oocyte retrieval and stored at -70 degrees C until assayed. IGF-I, IGF-II and IGFBP-3 concentrations were measured by radioimmunoassay and IGFBP-4 and PAPP-A by enzyme-linked immunosorbent assay. RESULTS: The duration of COS was significantly longer, and total dose of gonadotrophins used, serum estradiol (E(2)) levels on hCG day and the number of oocytes retrieved were significantly higher in the GnRHa long protocol group. The concentrations of FF IGF-II and IGFBP-4 were significantly higher, and the ratio of IGF-I/IGFBP-4 was significantly lower in the GnRHa long protocol group. Serum E(2) levels per mature follicle were not different between the two groups. CONCLUSIONS: Our data may indicate a difference of intrafollicular microenvironment between cycles using GnRHa long protocols and those using GnRHant protocols. However, the difference in microenvironment does not appear to result in a difference in clinical outcome. 相似文献
10.
Salobir B.; Prezelj J.; Meden-Vrtovec H.; Kocijancic A.; Osredkar J. 《Human reproduction (Oxford, England)》1996,11(10):2208-2210
The growth hormone (GH)/insulin-like growth factor-I (IGF-I)axis seems to play an important role in ovarian responsiveness.Recently IGF binding protein-3 (IGFBP-3) serum concentrationshave been reported to be a good marker of GH/IGF-I axis activity.In view of this finding, we measured IGFBP-3 serum concentrationsin 29 women undergoing in-vitro fertilization. We found a significantcorrelation among IGFBP-3 serum concentrations and markers ofovarian stimulation including efficacy index, serum oestradiolconcentrations and the number of follicles on the day of humanchoriomc gonadotrophin (HCG) administration. The results ofour study add additional evidence to the importance of the GH/IGF-Isystem in regulating ovarian responsiveness to gonadotrophinstimulation. 相似文献
11.
Insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations in fluid from human stimulated follicles 总被引:2,自引:5,他引:2
Oosterhuis GJ; Vermes I; Lambalk CB; Michgelsen HW; Schoemaker J 《Human reproduction (Oxford, England)》1998,13(2):285-289
Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP- 3)
play an important role in regulating follicle growth and maturation. We
have evaluated whether responsiveness to gonadotrophins during an in- vitro
fertilization (IVF) treatment is related to follicular fluid IGF- I and
IGFBP-3 concentrations. We also investigated if a difference is present in
IGF-I and IGFBP-3 concentrations between patients treated with human
menopausal gonadotrophin (HMG) and patients treated with highly purified
follicle stimulating hormone (FSH). We have measured IGF-I and IGFBP-3 in
follicular fluid from pre-ovulatory follicles in an IVF programme. All 70
patients were stimulated after being down- regulated with a
gonadotrophin-releasing hormone (GnRH) analogue. IGF-I concentrations in
follicular fluid were significantly inversely correlated with the number of
ampoules FSH administered and number of days of FSH administration, and
significantly correlated with the number of follicles aspirated. IGFBP-3
concentrations were not correlated with any other parameter measured nor
were IGF-I and IGFBP-3 concentrations correlated. IGFBP-3 concentrations
were significantly higher in patients receiving highly purified FSH
compared with patients receiving HMG (P < 0.005). These results are new
evidence that IGF-I concentration in follicular fluid is higher in women
who respond better to follicular stimulation, i.e. women who grow many
follicles, women who need a shorter duration of stimulation and women who
need fewer ampoules FSH before oocyte retrieval.
相似文献
12.
Genes or placenta as modulator of fetal growth: evidence from the insulin-like growth factor axis in twins with discordant growth 总被引:1,自引:0,他引:1
Westwood M Gibson JM Sooranna SR Ward S Neilson JP Bajoria R 《Molecular human reproduction》2001,7(4):387-395
To determine whether fetal growth is regulated by placental and/or fetal factors, we measured maternal and fetal concentrations of insulin-like growth factor-I (IGF-I), IGF-II and insulin-like growth factor binding protein-1 (IGFBP-1) (total and non-phosphorylated) in dichorionic (DC) and monochorionic (MC) twins with (DC, n = 13; MC, n = 12) or without (DC, n = 13; MC, n = 12) discordant birth weight. In the discordant MC pregnancy, growth-restricted (IUGR) twins had lower IGF-II concentrations (P < 0.001) but similar IGF-I concentrations compared to the appropriate for gestational age(AGA) co-twin. The differences in IGF-II concentrations showed a positive association with percentage birth weight discordance (r = 0.60; P < 0.05) in MC twins. In contrast, IUGR DC twins had lower IGF-I concentrations (P < 0.05) but similar IGF-II concentrations compared to the AGA co-twins. There was a positive correlation between IGF-I concentrations and birth weight (r = 0.47; P < 0.05) in DC twins. Total IGFBP-1 concentrations were higher in both MC and DC IUGR twins (P < 0.05) compared to AGA twins. A negative association was found between total IGFBP-1 concentrations and birthweight of both MC (r = 0.47; P < 0.05) and DC (r = 0.58; P < 0.01) twins. No such differences in IGF concentrations were found between concordant MC and DC twin pairs. The maternal IGF concentrations were comparable between the MC and DC groups. These data suggest that growth discordances of twins exposed to the same maternal environment may be due to variations in either IGF-I or IGF-II/IGFBP-1, depending upon the functioning of the placenta. 相似文献
13.
de Leo V la Marca A Morgante G Ciotta L Mencaglia L Cianci A Petraglia F 《Human reproduction (Oxford, England)》2000,15(11):2302-2305
The induction of ovulation by clomiphene could be the result of interaction of the drug at various levels: hypothalamus, pituitary and ovary. It was demonstrated that administration of clomiphene to women with polycystic ovarian syndrome (PCOS) is accompanied by a reduction in plasma concentrations of insulin-like growth factor-I (IGF-I). IGF-I seems to have an overall negative effect on normal folliculogenesis and ovulation. The aim of the present study was to evaluate the effect of clomiphene on plasma concentrations of IGF-I and IGF binding protein (IGFBP)-1 and on insulin resistance associated with PCOS. Fifteen patients diagnosed with PCOS were recruited. Clinical diagnosis was based on chronic oligomenorrhoea or amenorrhoea and hyperandrogenaemia. Clomiphene citrate was administered at a dose of 100mg/day to all women from day 5 to day 9 of the spontaneous or medroxyprogesterone acetate (MAP)-induced menstrual cycle. Blood sampling and a 2 h oral glucose loading test (75 g) were performed the day before and after the course of clomiphene. Ovulation was confirmed in 13/15 PCOS patients. Plasma concentrations of IGF-I decreased by 31.5% (434 +/- 84 versus 297 +/- 71 ng/ml; P: < 0.05) after 5 days of clomiphene therapy, whereas plasma concentrations of IGFBP-1 increased by approximately 28.1% (26.3 +/- 4 versus 36.6 +/- 7 ng/ml; P: < 0.05). This gave a 56.5% reduction in the IGF-I:IGFBP-1 ratio (21.9 versus 9.53). No significant changes in basal plasma concentrations of fasting insulin or area under the insulin curve were observed in response to oral loading. The present results show that clomiphene does not cause changes in insulin resistance associated with PCOS but reduces plasma concentrations of IGF-I and increases those of IGFBP-1, with a consequent marked reduction in the IGF-I:IGFBP-1 ratio. 相似文献
14.
Increasing evidence has implicated that insulin-like growth factors (IGFs), polypeptides structurally related to proinsulin, are involved in the function and development of the immune system. To probe the relevance of IGF binding protein 2 (IGFBP-2) in T-cell activation and proliferation, we studied the role of IGFBP-2 in anti-CD3 monoclonal antibody (mAb)-activated peripheral blood mononuclear cells (PBMCs). Secretion of IGF-I, IGF-II, and IGFBP-2 by PBMCs from healthy adult donors was determined by radioimmunoassays (RIAs). The PBMC proliferative response after stimulation with anti-CD3 mAb and exposure to increasing concentrations of IGF-I, IGF-II, IGFBP-2, and anti-IGFBP-2 were determined by bromodeoxyuridine enzyme-linked immunosorbent assay. Observations were tested for significance by paired t-tests. We demonstrate an increase in IGFBP-2 secretion associated with both activation of PBMC by anti-CD3 mAb and increasing cell density. Incubation with exogenous IGFBP-2 increased the proliferation of PBMCs, whereas anti-IGFBP-2 had an antiproliferative effect on PBMCs that was reversed by simultaneous exposure to IGFBP-2. The stimulatory activity of IGFBP-2 (1-10 ng/ml) on anti-CD3 mAb-activated PBMCs was similar to that of IGF-I and IGF-II (1-100 ng/ml), with the mean increase in PBMC proliferative response ranging between 150% and 160% for IGFBP-2 (p = 0.03), 150% and 170% for IGF-I (p < 0.01), 133%-161% for IGF-II (p < 0.01), and 157% and 175% for IGF-I + IGF-II (p < 0.01). Thus, our data strongly suggest a role for IGFBP-2 as a local growth factor contributing to the proliferation and activation of mononuclear cells. 相似文献
15.
Arthur I.D.; Anthony F.W.; Masson G.M.; Thomas E.J. 《Human reproduction (Oxford, England)》1994,9(8):1417-1420
Serum insulin-like growth factor binding protein-1 (IGFBP-1)concentrations were measured at the end of the proliferativephase in infertility patients undergoing normal menstrual cyclefrozen embryo transfer, exogenous hormone-supported frozen embryotransfer and in-vitro fertilization (IVF) treatment cycles.These patients were divided into five groups according to theirovarian follicular activity. The exogenous hormone-supportedfrozen embryo transfer group, who had no ovarian follicles,and the IVF groups (number of follicles ranging from 438)showed statistically higher serum IGFBP-1 concentrations whencompared to the normal menstrual cycle group (P0.01). Therewas no significant difference in the serum IGFBP-1 concentrationsbetween the exogenous hormone support frozen embryo transfergroup and the poor or normal response IVF groups (number offollicles ranging from 4 to 16). An IVF group that displayedan excessive response to our standard human menopausal gonadotrophinstimulation (>>20 mature follicles or oestradiol >>10000 pmol/1) showed a significantly higher serum IGFBP-1 concentrationwhen compared with the other groups (P = 0.001). This subgroupwas subsequently given a modified (follicle-stimulating hormone)stimulation regime which resulted in a significant reductionin serum IGFBP-1 concentrations (P << 0.05). There wasno correlation between serum oestradiol and IGFBP-1 overallor within the patient groups. We conclude that serum IGFBP-1concentrations in our down-regulated assisted conception cyclesdid not increase in line with ovarian follicular activity, unlessan excessive response was displayed. 相似文献
16.
D C Mynarcik R A Frost C H Lang K DeCristofaro M A McNurlan P J Garlick R T Steigbigel J Fuhrer S Ahnn M C Gelato 《Journal of acquired immune deficiency syndromes (1999)》1999,22(1):49-55
The purpose of this study was to characterize changes in the levels of insulin-like growth factor-I (IGF-I) and IGF binding proteins (BP) 1, 2, and 3 in HIV-infected adults throughout the course of their disease, and to assess the responsiveness of the IGF system components to growth hormone (GH) administration (6 mg/day) for 2 weeks. Healthy control study subjects (n = 10) were compared with patients who were either HIV-positive (n = 9), had AIDS without weight loss (n = 13), or had AIDS with >10% weight loss (n = 6), all of whom had been free of acute illness for at least 3 months. Under basal conditions, fasting serum concentrations of epinephrine, norepinephrine, cortisol, glucagon, insulin, IGF-I, and IGFBP-3 were not significantly different among the four groups. The serum concentrations of IGFBP-1 and IGFBP-2 were significantly higher in AIDS patients with wasting than in the other three groups (p < .05). In addition, there was a statistically significant positive correlation between the levels of IGFBP- 1 (p = .004) and IGFBP-2 (p = .03) and the stage of disease. Following GH administration, the serum concentrations of insulin and IGF-I were increased in all groups (p < .05). In addition, the increases in insulin levels correlated with stage of disease (p = .004). The responses of the IGFBPs were more variable. GH administration significantly increased the levels of IGFBP-3 in all groups except the patients with AIDS wasting, whereas the levels of IGFBP-1 were significantly decreased in controls and AIDS patients. These results demonstrate that there is a continuum of both elevations in the IGFBPs and altered metabolic responsiveness in patients infected with HIV that increases with the severity of the disease. These data also demonstrate that AIDS patients, who are free from secondary infection, respond to administration of GH by significantly increasing hepatic IGF-I production. 相似文献
17.
Rutanen EM 《Human reproduction (Oxford, England)》2000,15(Z3):173-181
Insulin-like growth factor (IGF) system is one of the growth factor systems that are believed to modulate steroid hormone actions in the endometrium through autocrine/paracrine mechanisms. IGF-I and IGF-II stimulate proliferation and differentiation, and maintain differentiated cell functions in several cell types in vitro. Endometrial stromal cells produce IGF-I and IGF-II as well as the high affinity IGF-binding proteins (IGFBP), whereas epithelial cells and, in a lesser amount, stromal cells contain cell membrane receptors for IGF. Oestrogen stimulates IGF-I gene expression, and IGF-II gene expression is associated with endometrial differentiation. The mRNA of six high affinity IGFBPs, which can modulate IGF actions, are expressed in human endometrium. The most abundant IGFBP in human endometrium is IGFBP-1, which is secreted by predecidualized/decidualized endometrial stromal cells in late secretory phase and during pregnancy. The primary negative regulator of IGFBP-1 production is insulin. IGFBP-1 competes with type I IGF receptor for binding of IGF in the endometrium and in cultured human trophoblastic cells. IGF-I mRNA is suppressed and mRNA encoding IGF-II and IGFBP-1 are consistently up-regulated in decidualized endometrium in women treated with the intrauterine levonorgestrel system (LNG-IUS). Strong cytoplasmic staining for IGFBP-1 was detected in decidualized endometrium in women using LNG-IUS for contraception or for endometrial protection during post-menopausal oestrogen replacement therapy. Simultaneously, oestrogen receptors were present, while progesterone receptors were hardly detectable in the endometrium by immunohistochemistry. The latter findings suggest that suppression of IGF-I action by IGFBP-1 may be one of the molecular mechanisms accounting for progestagenic and anti-oestrogenic effects of LNG-IUS in the endometrium. Consequently, examination of local IGF-I, IGF-II and IGFBP-1 expression might provide additional information when evaluating the effect of different progestins on the endometrium at the molecular level. 相似文献
18.
van der Meer M; de Boer JA; Hompes PG; Schoemaker J 《Human reproduction (Oxford, England)》1998,13(6):1465-1469
The aim of the present study was to determine the effect of octreotide, a
somatostatin analogue, on ovarian sensitivity for follicle stimulating
hormone (FSH) in patients with polycystic ovary syndrome (PCOS). As the
measure of ovarian sensitivity, the FSH threshold was determined in a
case-control set-up. Eleven patients with PCOS were treated with FSH in a
low dose step-up manner and subsequently received treatment with FSH
combined with octreotide. The FSH threshold was found to be significantly
higher during combined treatment. This increase was associated with a
decrease in insulin-like growth factor-I (IGF-I) and IGF binding protein-3
(IGFBP-3) concentrations during treatment with octreotide, but not with a
decrease in insulin concentrations. No differences were found between the
two regimens, in number of follicles, in oestradiol concentrations on the
day of human chorionic gonadotrophin (HCG) administration or in ovulation
rate. With both treatments, there was a very low rate of multifollicular
development. It can be concluded that octreotide lowers ovarian sensitivity
for FSH through suppression of IGF-I/IGFBP-3 in patients with PCOS.
However, this does not appear to affect follicular development during
gonadotrophin stimulation, because the latter is controlled to a high
degree by the use of a low dose step-up treatment schedule in these
patients.
相似文献
19.
D. Y. Lee 《Journal of Korean medical science》1998,13(1):17-20
Insulin-like growth factors (IGFs) are bound by several IGF-binding proteins (IGFBPs) that appear to regulate IGF transportation, receptor binding and action. In adult human serum, most of IGFs are bound in a 150 kDa complex which could not cross the capillary wall. We measured IGF-I and IGFBPs in chyle by radioimmunoassay and western ligand blot. The concentration of IGF-I in chyle was only 15% of the corresponding serum level and most of IGF-I was found in 50 kDa complex. The IGFBPs profile in chyle, especially IGFBP-3, was different from that of serum. The concentration of IGFBP-3 in chyle was much less than in serum and the size of glycosylated IGFBP-3 was different from that of serum. However, the size and relative amount of IGFBP-1 and -2 in chyle were similar to serum. This finding indicates that IGF-I and IGFBPs in chyle to a large extent originate in the vascular system and only the 50 kDa complex can cross the capillary barrier. 相似文献
20.
Juul A; Scheike T; Pedersen AT; Main KM; Andersson AM; Pedersen LM; Skakkebaek NE 《Human reproduction (Oxford, England)》1997,12(10):2123-2128
Few studies exist on the physiological changes in the concentrations of
growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding
proteins (IGFBP) within the menstrual cycle, and some controversy remains.
We therefore decided to study the impact of endogenous sex steroids on the
GH-IGF-IGFBP axis during the ovulatory menstrual cycle in 10 healthy women
(aged 18-40 years). Blood sampling and urinary collection was performed
every morning at 0800 h for 32 consecutive days. Every second day the
subjects were fasted overnight before blood sampling. Follicle stimulating
hormone, luteinizing hormone (LH), oestradiol, progesterone, IGF-I,
IGFBP-3, sex hormone-binding globulin, dihydroepiandrosterone sulphate and
GH were determined in all samples, whereas insulin and IGFBP-1 were
determined in fasted samples only. Serum IGF-I concentrations showed some
fluctuation during the menstrual cycle, with significantly higher values in
the luteal phase compared to the proliferative phase (P < 0.001). Mean
individual variation in IGF-I concentrations throughout the menstrual cycle
was 13.2% (SD 4.3; range 0.1-18.3%). There were no cyclic changes in
IGFBP-3 serum concentrations and no differences in IGFBP-3 concentrations
between the luteal and the proliferative phases. Mean individual variation
in IGFBP- 3 concentrations throughout the menstrual cycle was 8.8% (SD 2.7;
range 3.2-14.1). IGFBP-1 concentrations were inversely associated with
insulin concentrations, and showed a significant pre-ovulatory increase
that returned to baseline at the day of the LH surge. Fasting insulin
concentrations showed large fluctuations throughout the menstrual cycle
without any distinct cyclic pattern. No cyclic changes in urinary GH
excretion during menstrual cycle were detected. We conclude that, although
IGF-I concentrations are dependent on the phase of the menstrual cycle, the
variation in IGF-I concentrations throughout the menstrual cycle is
relatively small. Therefore, the menstrual cycle does not need to be
considered when evaluating IGF-I or IGFBP-3 serum values in women suspected
to have GH deficiency.
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