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.

Insulin-like growth factor-binding protein-3 expression and secretion by cultures of human prostate epithelial cells and stromal fibroblasts

1994 ◽  
Vol 141 (3) ◽  
pp. 535-540 ◽  
Author(s):  
R S Birnbaum ◽  
J L Ware ◽  
S R Plymate
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Conditioned Medium ◽  
Binding Protein ◽  
Human Prostate ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Cell Extracts ◽  
Prostate Epithelial Cells ◽  
Igfbp 3

Abstract Prostate-specific antigen (PSA) was recently shown to be an insulin-like growth factor-binding protein (IGFBP)-3 protease. However, only IGFBPs-2 and -4 have been identified in conditioned medium of prostate epithelial cells. Using cultures of human prostate epithelial and stromal fibroblastic cells, we examined conditioned medium and cell extracts for evidence of IGFBP-3 expression and secretion. Western ligand blotting of conditioned medium from epithelial or stromal cultures revealed the presence of IGFBPs in the molecular weight range 36–48 kDa, suggestive of IGFBP-3. Western immunoblots of these media confirmed the presence of IGFBP-3. Northern analyses of extracts of both stromal and epithelial cells showed a 2·5 kb band, the size of IGFBP-3 mRNA. We conclude that prostate cells express IGFBP-3 and that local proteolysis by PSA could modify this binding protein's actions in the prostate. Journal of Endocrinology (1994) 141, 535–540

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 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.

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.

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.

scholarly journals Upregulation of Cardiac Insulin-like Growth Factor-I Receptor by ACE Inhibition After Myocardial Infarction: Potential Role in Remodeling

2003 ◽  
Vol 51 (6) ◽  
pp. 831-839 ◽  
Author(s):  
Rachael G. Dean ◽  
Leon A. Bach ◽  
Louise M. Burrell
Keyword(s):  
Myocardial Infarction ◽  
Blood Pressure ◽  
Growth Factor ◽  
Cardiac Remodeling ◽  
Ace Inhibition ◽  
Border Zone ◽  
Positive Effects ◽  
Igf System ◽  
Igf I ◽  
Igfbp 3

This study evaluated the effects of angiotensin-converting enzyme (ACE) inhibition after myocardial infarction (MI) on cardiac remodeling and gene expression and localization of components (ligands, receptors, and binding proteins) of the cardiac insulinlike growth factor (IGF) system. After ligation of the coronary artery, rats were randomized to vehicle or ACE inhibitor (Captopril, 50 mg/kg/day) for 4 weeks. Blood pressure, cardiac remodeling, and components of the IGF system were localized in the heart using in situ hybridization (ISH) and immunohistochemistry (IHC). The average infarct size was 42%. There were regional differences in the expression of the IGF system after MI, with increased IGF-I mRNA abundance in the border (24-fold) and infarct (12-fold) and increased IGF-binding protein (IGFBP)-3 mRNA in all areas of the failing left ventricle (threefold). Captopril reduced blood pressure, attenuated cardiac remodeling, and caused a threefold increase in IGF-I receptor mRNA and protein in infarct, border zone, and viable myocardium ( p<0.01). Captopril had no effect on IGF-I mRNA but further increased IGFBP-3 mRNA and protein in the border zone, ( p<0.05). The changes in the cardiac IGF system following MI are highly localized, persist for at least 4 weeks, and can be modulated by ACE inhibition. These data suggest that the benefits of ACE inhibitors in attenuation of cardiac remodeling may be mediated in part through increased expression of the IGF-I receptor sensitizing the myocardium to the positive effects of endogenous IGF-I.

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