scholarly journals Co-administration of finasteride and the pure anti-oestrogen ICI 182,780 act synergistically in modulating the IGF system in rat prostate

2001 ◽  
Vol 171 (1) ◽  
pp. 109-118 ◽  
Author(s):  
H Huynh ◽  
L Alpert ◽  
MA Alaoui-Jamali ◽  
CY Ng ◽  
TW Chan
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cell ◽  
Tumour Progression ◽  
Ki 67 ◽  
Ici 182,780 ◽  
Prostate Weight ◽  
Igf System ◽  
Igf I ◽  
Rat Prostate ◽  
Igfbp 3

Prostate cancer is the most diagnosed invasive malignancy in males. Androgens and oestrogens have been implicated in the pathogenesis of prostate cancer. We report herein that the pure anti-oestrogen ICI 182,780 (ICI) reduces Ki-67 labelling index and IGF-I receptor levels in rat prostate. Increase of IGF-I mRNA and IGF-binding protein 3 (IGFBP-3) accumulation occur without any effect on prostate weight. Finasteride significantly decreases prostate weight and inhibits IGF-I gene expression. IGFBP-3 mRNA, Akt and phospho-Akt are not affected by finasteride. Co-administration of ICI plus finasteride reduces prostate weight by approximately 50% and causes acinar dilation with decreased luminal epithelial cell thickness. The acinar epithelial cells became atrophic and inactive with minimal cytoplasm. We also demonstrate a synergistic effect of ICI and finasteride on induction of IGFBP-3 accumulation and inhibition of Akt phosphorylation. Because the IGF and IGFBP-3 system plays an important role in prostate epithelial cell proliferation, apoptosis and tumour progression, the inhibitory effects of finasteride and ICI on IGF system may contribute to their anti-proliferative activity. These observations support a potential use of ICI in conjunction with finasteride in the prevention and/or treatment of prostate cancer.

scholarly journals Regulation of proliferation of prostate epithelial cells by 1,25-dihydroxyvitamin D3 is accompanied by an increase in insulin-like growth factor binding protein-3

2001 ◽  
Vol 170 (3) ◽  
pp. 609-618 ◽  
Author(s):  
CC Sprenger ◽  
A Peterson ◽  
R Lance ◽  
JL Ware ◽  
RH Drivdahl ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Human Prostate ◽  
Dihydroxyvitamin D3 ◽  
Prostate Epithelial Cell ◽  
Igf System ◽  
Prostate Epithelial Cells ◽  
Igf I ◽  
Igfbp 3

The biologically active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to regulate the proliferation of human prostate epithelial cell lines. Since the insulin-like growth factor (IGF) system is involved in the transformation process of epithelial cells, the following study was undertaken to determine if the IGF system, in particular IGF binding protein-3 (IGFBP-3), is altered by 1,25-(OH)2D3 in normal prostate epithelial cells as part of a mechanism for inhibition of transformation. Two cell systems were used in this study: (1) primary cultures of benign human prostate epithelial cells (PECs) and (2) an SV40-T immortalized prostate epithelial cell line (P153) that is non-tumorigenic. 1,25-(OH)2D3 was added to parallel sets of PECs and P153 cells in addition to the presence or absence of IGF-I or des(1-3)IGF-I. Treatment with 1,25-(OH)2D3 resulted in significant growth inhibition of both PECs and P153 cells. Furthermore, 1,25-(OH)2D3 inhibited IGF-induced proliferation, but this was partially reversed by high concentrations of IGF-I. Western ligand blots of condition media demonstrated a significant increase in IGFBP-3; likewise Northern blots demonstrated an increase in mRNA for IGFBP-3. Proliferation assays using an antibody designed to block the IGF-independent effects of IGFBP-3 failed to reverse the inhibitory effect of 1,25-(OH)2D3. Thus, IGFBP-3 acts in an IGF-dependent manner to inhibit cell growth of benign prostate epithelial cells.

Physical capacity influences the response of insulin-like growth factor and its binding proteins to training

2002 ◽  
Vol 93 (5) ◽  
pp. 1669-1675 ◽  
Author(s):  
Lars Rosendal ◽  
Henning Langberg ◽  
Allan Flyvbjerg ◽  
Jan Frystyk ◽  
Hans Ørskov ◽  
...  
Keyword(s):  
Growth Factor ◽  
Physical Training ◽  
Binding Proteins ◽  
Insulin Like Growth Factor ◽  
Initial Training ◽  
Serum Samples ◽  
Fitness Level ◽  
Igf System ◽  
Igf I ◽  
Igfbp 3

The influence of initial training status on the response of circulating insulin-like growth factor (IGF) and its binding proteins (IGFBP) to prolonged physical training was studied in young men. It was hypothesized that highly standardized training would result in more extensive changes in the circulating IGF system in untrained subjects because of lower fitness level. Seven untrained (UT) and 12 well-trained (WT) individuals performed 11 wk of intense physical training (2–4 h daily). Fasting serum samples were analyzed for total and free IGF-I and -II, for IGFBP-1 to -4, as well as for IGFBP-3 proteolysis. Eleven weeks of physical training resulted in decreased levels of total IGF-I, free IGF-I, and IGFBP-4 in both the UT and WT groups. In the UT group, IGFBP-2 increased, IGFBP-3 decreased [from 4,255 ± 410 (baseline) to 3,896 ± 465 (SD) μg/l ( week 4); P < 0.05], and IGFBP-3 proteolysis increased [from 28 ± 8% (baseline) to 37 ± 7% ( week 4) and 39 ± 12% ( week 11); P < 0.05], whereas no significant changes were found in the WT group. In conclusion, intense physical training results in a marked influence on the IGF system and its binding proteins with generally more extensive changes seen in the untrained individuals. Also, prolonged physical training resulted in increased IGFBP-3 proteolysis in previously untrained individuals only, indicating that intense physical training affects trained and untrained individuals differently.

scholarly journals Insulin-Like Growth Factor I Is Not a Useful Marker of Prostate Cancer in Men with Elevated Levels of Prostate-Specific Antigen1

2000 ◽  
Vol 85 (8) ◽  
pp. 2744-2747
Author(s):  
Patrik Finne ◽  
Anssi Auvinen ◽  
Hannu Koistinen ◽  
Wan-Ming Zhang ◽  
Liisa Määttänen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Cancer Risk ◽  
Prostate Volume ◽  
Specific Antigen ◽  
Elevated Serum ◽  
Prostate Cancer Risk ◽  
Factor I ◽  
Igf I ◽  
Igfbp 3

High serum levels of insulin-like growth factor I (IGF-I) and low levels of IGF-binding protein-3 (IGFBP-3) have been shown to correlate with increased prostate cancer risk. To evaluate this, IGF-I, IGFBP-3, and prostate-specific antigen (PSA) were measured in serum from 665 consecutive men (179 with prostate cancer), aged 55–67 yr, with elevated serum prostate-specific antigen (PSA; ≥4 μg/L) in a screening trial. Men in the highest quartile of IGF-I levels had an odds ratio (OR) for prostate cancer of 0.50 [95% confidence interval (CI) 0.26–0.97] when adjusting for serum IGFBP-3. IGFBP-3 itself was not significantly associated with prostate cancer risk (OR, 1.24; 95% CI, 0.68–2.24). Prostate volume was larger in men without than in those with prostate cancer (P &lt; 0.001), and after adjustment for prostate volume, the negative association between serum IGF-I and prostate cancer risk was no longer significant (OR, 0.57; 95% CI, 0.28–1.16). In screen-positive men with elevated serum PSA, serum IGF-I is not a useful diagnostic test for prostate cancer, but it may be associated with benign prostatic hyperplasia and enlargement.

scholarly journals Expression of the insulin-like growth factor (IGF) system in the bovine oviduct at oestrus and during early pregnancy

Reproduction ◽  
2002 ◽  
pp. 859-868 ◽  
Author(s):  
PG Pushpakumara ◽  
RS Robinson ◽  
KJ Demmers ◽  
GE Mann ◽  
KD Sinclair ◽  
...  
Keyword(s):  
Embryo Development ◽  
Expression Patterns ◽  
Muscular Activity ◽  
Early Embryo ◽  
Oestrous Cycle ◽  
Mammalian Embryo ◽  
Igf System ◽  
Igf I ◽  
Igfbp 3

Early mammalian embryo development in vitro can be enhanced by co-culture with oviductal cells and by the addition of insulin-like growth factors (IGFs). This study examined the expression patterns of the oviductal IGF system in cattle in relation to the number of days after oestrus and the presence or absence of embryos. Oviducts were collected from: (i) 66 nulliparous heifers on day 3, day 6 or day 16 after insemination and from (ii) ten non-pregnant, lactating cows on day 0 or day 1 of the oestrous cycle. Oviducts were coiled, frozen whole and sectioned for in situ hybridization. Expression patterns of mRNAs encoding IGF-I, IGF-II, type 1 IGF receptor (IGF-1R), and the IFG binding proteins (IGFBP)-1, -3 and -5 were determined from autoradiographs. Separate measurements were made for the mucosa and muscle layers of the infundibulum, ampulla and isthmus. None of the parameters measured differed between heifers with or without the presence of an embryo. mRNAs encoding IGF-I and IGF-1R were present in the mucosa and muscle of all three oviductal regions, and the highest value of IGF-I mRNA was measured in heifers on day 3. IGF-II mRNA was expressed predominantly in the muscle wall. IGFBP-1 mRNA was not detectable, whereas mRNAs encoding IGFBP-3 and -5 were expressed in both the muscle and mucosa. IGFBP-3 expression was higher in cows on day 0 and day 1 of the oestrous cycle than in heifers on day 3, day 6 and day 16 after insemination. A peak of IGFBP-5 expression was reached on day 6. Locally or systemically produced IGFs, regulated by IGFBPs, may act directly on the embryo or indirectly via modulation of oviductal secretions and muscular activity to influence the success of early embryo development.

scholarly journals Dietary intake and the insulin-like growth factor system: effects of migration in two related populations in India and Britain with markedly different dietary intake

2005 ◽  
Vol 8 (6) ◽  
pp. 620-627 ◽  
Author(s):  
AH Heald ◽  
R Sharma ◽  
SG Anderson ◽  
A Vyas ◽  
K Siddals ◽  
...  
Keyword(s):  
Growth Factor ◽  
Dietary Intake ◽  
Total Energy ◽  
Macronutrient Intake ◽  
Fat Intake ◽  
Insulin Like Growth Factor ◽  
Igf System ◽  
Igf I ◽  
Total Fat ◽  
Igfbp 3

AbstractBackgroundThe insulin-like growth factor (IGF) system is implicated in the pathogenesis of diabetes and cardiovascular disease.ObjectiveWe report the effects of total energy intake on the IGF system in two populations with markedly different dietary macronutrient intake and cardiovascular event rate.Design, subjects and settingDietary macronutrient intake was measured in a specific Gujarati migrant community in Sandwell, UK (n = 205) compared with people still resident in the same villages of origin in India (n = 246). Fasting IGF-I, IGF-binding protein (IGFBP)-1 and IGFBP-3, insulin and glucose (0 and 2-hour) were measured.ResultsTotal energy and total fat intake were higher in UK migrants, as were IGFBP-3 and IGF-I (mean (95% confidence interval): 145.9 (138.1–153.6) vs. 100.9 (94.6–107.3) ng ml-1; F = 76.6, P < 0.001). IGFBP-1 was lower in UK migrants (29.5 (25.9–33.0) vs. 56.5 (50.6–62.5) μg l-1; F = 48.4, P < 0.001). At both sites, IGF-I correlated positively with total energy (Spearman's ρ = 0.45, P < 0.001) and total fat (ρ = 0.44, P < 0.001) as did IGFBP-3 with total energy (ρ = 0.21, P < 0.05) and fat (ρ = 0.26, P < 0.001). Conversely, in Indian Gujaratis, IGFBP-1 fell with increasing total energy (ρ = -0.27, P < 0.001) and fat intake (ρ = -0.26, P < 0.01) but not in UK Gujaratis. Multiple linear regression modelling showed that increasing quartiles of fat intake were associated with higher IGF-I (β = 0.42, P = 0.007) independent of age, body mass index, plasma insulin, fatty acids and 2-hour glucose.ConclusionIn these genetically similar groups, migration to the UK and adoption of a different diet is associated with marked changes in the IGF system, suggesting that environmental factors profoundly modulate serum concentrations and actions of IGFs.

Acute response of IGF-I and IGF binding proteins induced by thermal injury

2000 ◽  
Vol 278 (6) ◽  
pp. E1087-E1096 ◽  
Author(s):  
Charles H. Lang ◽  
Xiaoli Liu ◽  
Gerald J. Nystrom ◽  
Robert A. Frost
Keyword(s):  
Plasma Concentration ◽  
Binding Proteins ◽  
Thermal Injury ◽  
Igf Binding Proteins ◽  
Igf System ◽  
Significant Difference ◽  
Mrna Transcripts ◽  
Igf I ◽  
Igf Binding ◽  
Igfbp 3

Previous studies demonstrate that thermal injury decreases circulating levels of insulin growth factor I (IGF-I) and alters the plasma concentration of several IGF binding proteins (IGFBP), but the mechanisms for these alterations have not been elucidated. In the current study, a 30% total body surface area full-thickness scald burn was produced in anesthetized rats, and animals were studied 24 h later. The plasma concentration of both total and free IGF-I was decreased (38 and 65%, respectively) in burn rats compared with values from time-matched control animals. Thermal injury decreased the IGF-I peptide content in liver ∼40%, as well as in fast-twitch skeletal muscle (56–69%) and heart (28%). In contrast, IGF-I content in kidney was elevated by 36% in burn rats. Northern blot analysis of liver indicated that burn decreased the expression of small (1.7- and 0.9- to 1.2-kb) IGF-I mRNA transcripts but increased the expression of the 7.5-kb transcript. In contrast, there was a coordinate decrease in all IGF-I mRNA transcripts in muscle and kidney of ∼30%. For liver, muscle, and kidney, there was no significant difference in the expression of growth hormone receptor mRNA between control and burn rats. Thermal injury increased plasma IGFBP-1 levels, and this change was associated with increased IGFBP-1 mRNA in both liver and kidney. IGFBP-3 levels in plasma were concomitantly decreased by burn injury. This change was associated with a reduction in IGFBP-3 mRNA in liver but an increased expression of IGFBP-3 in kidney and muscle. Thermal injury also decreased the concentration of the acid-labile subunit (ALS) in plasma and ALS mRNA expression in liver. Finally, hepatic expression of IGFBP-related peptide-1 was increased twofold in liver but was unchanged in kidney or muscle of burn rats. These results characterize burn-induced changes in various components of the IGF system in select tissues and thereby provide potential mechanisms for alterations in the circulating IGF system and for changes in tissue metabolism.

Effect of a high maternal dietary intake during mid-gestation on components of the utero-placental insulin-like growth factor (IGF) system in adolescent sheep with retarded placental development

Reproduction ◽  
2000 ◽  
pp. 407-416 ◽  
Author(s):  
TS Gadd ◽  
RP Aitken ◽  
JM Wallace ◽  
DC Wathes
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Maternal Nutrition ◽  
Limit Of Detection ◽  
Receptor Expression ◽  
Insulin Like Growth Factor ◽  
Placental Development ◽  
Igf System ◽  
Igf I ◽  
Igfbp 3

The aim of the present study was to investigate the effects of administering a high plane diet during early to mid-gestation on the uterine and placental insulin-like growth factor (IGF) system and on systemic IGF-I concentrations in pregnant adolescent ewes with restricted placental growth. Embryos recovered from superovulated ewes inseminated by a single sire were transferred in singleton to the uterus of adolescent recipients. After transfer ewes were offered a high (H) or moderate (M) amount of a complete diet calculated to promote rapid or normal maternal growth rates, respectively. Five ewes from each group were switched from either M to H or H to M diets at day 52 of gestation. Maternal and fetal blood samples and placental tissues were collected from all animals at day 104. Ewes on the high plane diet from mid-gestation (HH, MH groups) had restricted placental mass (P < 0.01) and tended to have smaller fetuses. This was associated with increased maternal plasma IGF-I concentrations (P < 0.001). The pattern of expression of components of the IGF system in the uterus and placenta was studied by in situ hybridization. IGF-I mRNA concentrations were below the limit of detection. IGF-II mRNA expression was high in the fetal mesoderm and present in maternal stroma, but was not influenced by nutritional treatment. In contrast, IGF binding protein 1 (IGFBP-1) mRNA expression was higher (P < 0.05) and IGFBP-3 mRNA expression was lower (P < 0.05) in the endometrial glands of ewes in HH and MH groups. In the fetal trophoblast, IGFBP-3 mRNA expression was higher in the MH group. Type 1 IGF receptor expression was increased (P < 0. 01) in the luminal epithelium of the HM group and IGFBP-2 mRNA expression was highest in the placentome capsule of ewes in the HH group. Together, these results indicate that reprogramming of the uterine and placental IGF axis by maternal nutrition could contribute to placental growth retardation in growing adolescent sheep.

High Levels of Circulating Insulin-Like Growth Factor-I Increase Prostate Cancer Risk: A Prospective Study in a Population-Based Nonscreened Cohort

2004 ◽  
Vol 22 (15) ◽  
pp. 3104-3112 ◽  
Author(s):  
Pär Stattin ◽  
Sabina Rinaldi ◽  
Carine Biessy ◽  
Ulf-Håkan Stenman ◽  
Göran Hallmans ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
Population Based ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Bottom Quartile ◽  
Igf I ◽  
Igfbp 3

PurposeInsulin-like growth factor-I (IGF-I) stimulates proliferation and inhibits apoptosis in prostate cancer cells, and IGF-I has been associated with increased prostate cancer risk in some, but not all, epidemiologic studies.Subjects and MethodsWe extended our previous case-control study nested in the Northern Sweden Health and Disease Cohort, a population-based cohort from a region where little prostate specific antigen (PSA) screening is done. Levels of IGF-I and IGF binding protein-3 (IGFBP-3) were measured in prediagnostic blood samples from a total of 281 men who were subsequently diagnosed with prostate cancer after recruitment (median, 5 years after blood collection) and from 560 matched controls.ResultsLogistic regression analyses showed increases in prostate cancer risk with increasing plasma peptide levels, up to an odds ratio (OR) for top versus bottom quartile of IGF-I of 1.67 (95% CI, 1.02 to 2.71; Ptrend= .05), which was attenuated after adjustment for IGFBP-3 to an OR of 1.47 (95% CI, 0.81 to 2.64; Ptrend= .32). For men younger than 59 years at recruitment, OR for top versus bottom quartile of IGF-I was 4.12 (95% CI, 1.01 to 16.70; Ptrend= .002), which was significantly stronger than for men older than 59 years (Pinteraction= .006). For men with advanced cancer, OR for top versus bottom quartile of IGF-I was 2.87 (95% CI, 1.01 to 8.12; Ptrend= .10).ConclusionOur data add further support for IGF-I as an etiologic factor in prostate cancer and indicate that circulating IGF-I levels measured at a comparatively young age may be most strongly associated with prostate cancer risk.

scholarly journals Genetic Polymorphisms in IGF-I and IGFBP-3 Are Associated with Prostate Cancer in the Chinese Population

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e85609 ◽  
Author(s):  
Jian Qian ◽  
Hai Zhou ◽  
Jiawei Chen ◽  
Qi Ding ◽  
Qiang Cao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genetic Polymorphisms ◽  
Chinese Population ◽  
Igf I ◽  
Igfbp 3
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