Biphasic Kinetics of IGF-I and IGFBP-3 in Response to Military Field Training in Brazilian Air Force Recruits.

INTRODUCTION: Insulin-like growth factor type I (IGF-I) has gained considerable notoriety in military training, primarily because it is responsible for energy deficits and sensitive to an inadequate protein intake, which are situations that are commonly experienced in specific military operations. Therefore, this study aimed to assess the kinetics of IGF-I and insulin-like growth factor binding protein type 3 (IGFBP-3) in a 4-day military field training exercise. MATERIALS AND METHODS: The sample comprised 12 male soldiers (21.71 ± 1.64 years). Changes were assessed at 3 times: time 1-basal (control week); time 2-after specific military field training; and time 3-1 week after the specific training (control week). Changes in body composition and serum levels of IGF-I and IGFBP-3 were observed. RESULTS: The main finding of this study was it verified the biphasic kinetics of both IGF-I and IGFBP-3 at the 3 times observed, that is, a significant drop from time 1 (basal-IGF-I: 189 ng/mL and IGFBP-3: 4.71 mg/L) to time 2 (immediately after military training-IGF-I: 162 ng/mL and IGFBP-3: 4.08 mg/L) and a subsequent recovery of these markers, with a significant increase from time 2 (immediately after military training) to time 3 (a week after military training-IGF-I: 199 ng/mL and IGFBP-3: 4.96 mg/L). CONCLUSIONS: It can be concluded that IGF-I and IGFBP-3 levels respond quickly to the stimuli caused by military training, especially after specific field training. However, the same markers quickly return to their basal values after this type of training finishes, simply by following the daily routine of the battalion in the control weeks, with no specific intervention being necessary.

Oral Administration of Microencapsulated B. Longum BAA-999 and Lycopene Modulates IGF-1/IGF-1R/IGFBP3 Protein Expressions in a Colorectal Murine Model.

The Insulin-like growth factor-I/Insulin-like growth factor-I receptor (IGF-1/IGF-1R) system is a major determinant in colorectal cancer (CRC) pathogenesis. Probiotics (Bifidobacterium longum, BF) and lycopene (LYC) have been individually researched for their beneficial effects in the prevention of CRC. However, the effect of a combined treatment of microencapsulated BF and LYC on IGF-1/IGF-1R/IGFBPs (Insulin-like growth factor-binding proteins) expression in an azoxymethane (AOM)-dextran sulfate sodium (DSS)-induced CRC model have not been demonstrated. BF was microencapsulated by the spray drying technique, with high viability, and daily gavaged with LYC for 16 weeks to CD-1 mice in an AOM-DSS model. The results indicated that BF- and BF + LYC-treated groups had significantly lower inflammation grade, tumor incidence (13-38%) and adenocarcinoma (13-14%) incidence compared to the AOM + DSS group (80%), whereas LYC treatment only protected against inflammation grade and incidence. Caecal, colonic and fecal pH and ß-glucuronidase (ß-GA) values were significantly normalized by BF and LYC. Similarly, BF and BF + LYC treatments significantly reduced both the positive rate and expression grade of IGF-1 and IGF-1R proteins and normalized Insulin-like growth factor-binding protein-3 (IGFBP3) expression. Based on intestinal parameters related to the specific colon carcinogenesis in an AOM-DSS-induced model, LYC and microencapsulated BF supplementation resulted in a significant chemopreventive potential through the modulation of IGF-1/IGF-1R system.

Intramammary infusion of Panax ginseng extract in the bovine mammary gland at cessation of milking modifies components of the insulin-like growth factor system during involution.

The objective of this study was to evaluate the effects of a single intramammary infusion of Panax ginseng extract (GS) on insulin-like growth factors (IGF) in bovine mammary gland during early involution. Eight mammary quarters from six nonpregnant cows in late lactation were infused with 10 mL of ginseng extract solution (3 mg/mL), six quarters were treated with 10 mL of placebo (vehicle alone) and six quarters were maintained as uninoculated controls. Milking was interrupted after infusion. Concentrations of IGF1 in mammary secretions were higher in GS-treated quarters than in placebo and uninoculated control quarters at 24, 48 and 72 h post-treatment (p<0.05). Treatment with GS did not affect mammary secretion of IGF2 (p=0.942). At 7 d of post-lactational involution, a decrease of immunostained area and mRNA expression for IGF1 was observed in mammary tissue of GS-treated quarters compared with placebo-treated quarters and uninoculated controls (p<0.05). The IGF2 immunostained area and mRNA expression for this growth factor were not affected by GS treatment (p=0.216 and p=0.785, respectively). An increase in protein levels and mRNA expression in mammary tissue of IGFBP3, IGFBP4 and IGFBP5 was observed in GS-treated quarters compared with placebo-treated quarters and uninoculated controls (p<0.05). These results provide evidence that intramammary inoculation of GS extract at cessation of milking may promote early mammary involution through the inhibition of IGF1 local production and bioavailability.

[Management of the growth hormone (GH)-treated patients with diagnosis of GH deficiency (DGH) during transition from childhood to adulthood]. / Condução do tratamento com hormônio de crescimento (GH) nos pacientes com diagnóstico de deficiência GH (DGH) durante o período de transição da criança para o adulto.

Growth hormone (GH) has many beneficial effects in patients with childhood-onset GH deficiency (GHD) in addition to its promotion of linear growth. The discontinuation of GH treatment in GHD patients, during the transition from childhood to adulthood, induces significant unfavorable changes in body composition, skeletal integrity, exercise capacity, and an adverse cardiovascular risk profile. These changes are reversed after the resumption of GH treatment. As the benefits of continuing GH therapy into adulthood has been well established, it is possible that GH replacement therapy will not be stopped once growth has been completed, but it will continue into adult life. Considering that a high proportion of patients with diagnosis of DGH in childhood are no longer GHD in adolescence, the GH status must be retested when growth is completed. Other factors such as clinical history, GH response in childhood, hipotalamic-pituitary MRI and IGF-1 concentration must be considered. Reconfirmation of GHD diagnosis through stimulation testing is usually required, unless there is a proven genetic or structural lesion persistent from childhood.

Breast cyst fluids increase the proliferation of breast cell lines in correlation with their hormone and growth factor concentration.

OBJECTIVE AND DESIGN: Gross cystic disease (GCD) of the breast is reported to occur in 7% of women in the developed world and, although not premalignant, is thought to be associated with an increased risk of breast cancer. Hormone and growth factor concentration levels were measured in breast cyst fluid (BCF) to correlate them with their mitogenic activity in tumour (MCF-7) or nontransformed (MCF-10A) cells. RESULTS: Oestradiol (E2), oestrone (E1), E2-sulfate (E2-S), E1-sulfate (E1-S) and epidermal growth factor (EGF) concentrations were, as expected, significantly higher in type I than in type II cysts, while transforming growth factor-beta 2 (TGF-beta2) showed higher levels in type II cysts. Fifty per cent of the BCF samples stimulated [3H]-thymidine incorporation into MCF-7 cells while 34.5% inhibited this parameter. In MCF-10A cells, most BCF samples were stimulatory (85%). E2, E1 and EGF concentrations in BCF samples correlated significantly and positively with cell proliferation in MCF-7 cells, whereas a significant negative correlation was found for TGF-beta2. In MCF-10A cells, only E2-S and E1-S exhibited significant positive correlation, whereas a significant negative correlation was found for TGF-beta2. Progesterone (Pg), E2 and EGF incubated under the same conditions had a stimulatory effect on [3H]-thymidine incorporation into MCF-7 cells, whereas TGF-beta2 inhibited this parameter. Pg, E2, E1 and EGF significantly stimulated this parameter in MCF-10A cells. CONCLUSIONS: The stimulatory action of BCF on cell proliferation in a model of human breast epithelial cells could partly explain the increased incidence of breast cancer in cyst-bearing women.

Different states of clinical control are associated with changes in IGF-I and IGFBPs in children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

OBJECTIVE: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is characterized by high androgen levels, ambiguous genitalia or premature pubarche, increased height velocity and skeletal maturation. Considering the possibility of changes in the IGF system components depending on the state of clinical control, the objective of the present study was to analyse serum IGF-I, IGF-II and IGFBP levels in children with 21-OHD under two states of clinical control. PATIENTS AND DESIGN: We studied 12 prepubertal children with 21-OHD CAH aged 4.0 +/- 0.7 years. They were classified as good (GC) or poor control (PC) based on growth rate, signs of adrenal insufficiency or Cushing syndrome, progression of sexual characteristics and serum androgens levels. Blood samples were obtained from each patient in two different states of clinical control (GC and PC) for biochemical measurements. MEASUREMENTS: IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 were determined by immunoassays. IGFBPs were also analysed by Western ligand blotting (WLB). RESULTS: Levels of IGF-I (P = 0.03) and IGFBP-3 (P = 0.01) were higher in GC than in PC while IGFBP-1 (P = 0.004) concentrations were lower in GC patients. A trend towards higher levels of IGF-II (P = 0.08) and lower levels of IGFBP-2 (P = 0.08) was observed in GC children. Increased IGFBP-4 band intensity was observed in GC children (P = 0.03). CONCLUSION: Higher levels of IGF-I, IGFBP-3 and IGFBP-4, but lower levels of IGFBP-1, were associated with better control in children with 21-OHD CAH. These findings are different from those observed in children with other causes of increasing androgens levels and are likely to be related to the insufficient glucocorticoid status.

Leptin levels and IgF-binding proteins in malnourished children: effect of weight gain.

OBJECTIVES: Although it is well known that leptin reflects body fat content in adults, the regulation of leptin levels during childhood malnutrition is poorly understood. Insulin-like growth factor I (IGF-I) and the IGF-binding proteins (IGFBPs) may play important roles in the regulation of body composition. We investigated the relation between leptin, IGF-I, and IGFBPs in children with protein-energy malnutrition (PEM; before and after recovering 10% of their initial body weights) in comparison with well-nourished children. METHODS: Fifteen PEM and 16 healthy children were studied on admission and after 10% weight gains in the malnourished group. Leptin was measured with radioimmunoassay, IGF-I and IGFBPs were measured with immunoradiometric assay. RESULTS: Patients with PEM had a significantly lower body mass index and percentage of body fat than did the control children. Before weight gain, leptin, IGF-I, and IGFBP-3 were significantly lower and IGFBP-1 was elevated in the malnourished group compared with the control group. Among PEM patients, after 10% weight gains, the levels of leptin, IGF-I, and IGFBP-3 were significantly higher and IGFBP-1 significantly lower compared with the control group. Leptin correlated significantly with IGF-I in the normal children (r(s) = 0.86, P < 0.005). On admission, no correlation was observed between leptin and IGF-I (r(s) = 0.08, P < 0.16) and between leptin and IGFBP-3 (r(s) = 0.02, P < 0.27) in the malnourished group, but those levels improved after 10% recovery of their body weights (r(s) = 0.47, P < 0.002 and r(s) = 0.42, P < 0.005, respectively). In the PEM group, IGF-I correlated significantly with IGFBP-3 when the children gained weight (before: r(s) = 0.006, P < 0.31; after: r(s) = 0.32, P < 0.01). Our study showed results similar to those of anorexia nervosa studies, but the normalization of study variables was obtained in considerable less time for the same weight gain. CONCLUSIONS: The main finding of this study was that, after refeeding with only a 10% weight gain, the PEM children normalized their leptin, IGF-I, and IGFBP-3 levels. These results provide evidence that leptin can function as link between this hormonal response and improved nutrition status.

Effect of nitric oxide on the expression of insulin-like growth factors and the insulin-like growth factor binding proteins throughout the lifespan of the human corpus luteum.

The presence of insulin-like growth factors (IGF), IGF binding proteins (IGFBP) and IGF receptor type 1 (IGF-IR) in the human corpus luteum was investigated by examining the expression and production of related proteins throughout the lifespan of the corpus luteum and the action of nitric oxide upon their production. The expression of proteins in corpora lutea from the early, mid-and late luteal phases was assessed by immunohisto-chemistry, evaluated by a semi-quantitative analysis and the functional study was performed in corpus luteum explants incubated with nitric oxide donors. IGF-I and -II and IGFBP-1 and -3 were measured in the culture media by specific immunoassays. The results showed that IGF-I and -II, IGFBP-1 to -6 and IGF-IR were detected in the human corpus luteum throughout the luteal phase. Moreover, the expression and production of IGF-I and IGFBP-1 increased progressively from corpora lutea from the early to late luteal phases (P < 0.05), whereas the expression and production of IGFBP-2, -4 and -5 were significantly higher in corpora lutea from the mid-luteal phase (P < 0.05). No differences were observed in the expression of IGF-II, IGFBP-3 and -6 and IGF-IR throughout the lifespan of the corpus luteum. However, functional studies showed that nitric oxide donors elicited a stimulatory action on production of IGF-I in corpora lutea from the early luteal phase (80%) and on production of IGFBP-1 in corpora lutea from the late luteal phase (50%) (P < 0.05), whereas production of IGF-II and IGFBP-3 was not affected by nitric oxide. In conclusion, the components of the IGF-IGFBP system are expressed in the human corpus luteum throughout its lifespan. Nitric oxide regulates IGF-I and IGFBP-1 production, indicating that the growth factors may serve, at least in part, as mediators of the action of nitric oxide in the human corpus luteum.