Cows with different Insulin-like Growth Factor-I (IGF-I) concentrations showed comparable expression levels of hepatic growth hormone receptor (GHR). Suppressor of cytokine signaling 2 (SOCS2), could be responsible for additional inhibition of the GHR signal cascade. The aims were to monitor cows with high or low antepartal IGF-I concentrations (IGF-I(high) or IGF-I(low)), evaluate the interrelationships of endocrine endpoints, and measure hepatic SOCS2 expression. Dairy cows (n = 20) were selected (240 to 254 days after artificial insemination (AI)). Blood samples were drawn daily (day -17 until calving) and IGF-I, GH, insulin, thyroid hormones, estradiol, and progesterone concentrations were measured. Liver biopsies were taken (day 264 +/- 1 after AI and postpartum) to measure mRNA expression (IGF-I, IGFBP-2, IGFBP-3, IGFBP-4, acid labile subunit (ALS), SOCS2, deiodinase1, GHR1A). IGF-I concentrations in the two groups were different (p < 0.0001). However, GH concentrations and GHR1A mRNA expression were comparable (p > 0.05). Thyroxine levels and ALS expression were higher in the IGF-I(high) cows compared to IGF-I(low) cows. Estradiol concentration tended to be greater in the IGF-I(low) group (p = 0.06). It was hypothesized that low IGF-I levels are associated with enhanced SOCS2 expression although this could not be decisively confirmed by the present study.
Animals ; Cattle ; Estradiol/blood ; Female ; Growth Hormone/blood ; Insulin/blood ; Insulin-Like Growth Factor Binding Protein 2/analysis ; Insulin-Like Growth Factor Binding Protein 3/analysis ; Insulin-Like Growth Factor Binding Protein 4/analysis ; Insulin-Like Growth Factor I/*analysis/physiology ; Liver/chemistry ; Pregnancy/metabolism/physiology ; Pregnancy, Animal/*metabolism/physiology ; Progesterone/blood ; Suppressor of Cytokine Signaling Proteins/analysis ; Thyroid Hormones/blood

OBJECTIVEInsulin-like grouth factor-1 (IGF-1) is polypetide hormone that has demonstrated effects on neural cells. Up to now, there is few reports about the relation between serum IGF-1 and brain damage in neonates with hyperbilirubinemia. This study explored the potential role of serum IGF-1 in neonatal hyperbilirubinemia.

METHODSSerum levels of IGF-1 were measured using ECLIA in 57 term neonates with hyperbilirubinemia and 25 normal term neonates. Meanwhile, total serum bilirubin (TSB), unconjugated bilirubin (USB) and serum albumin (ALB) contents were measured by the automatic biochemistry analyzer and the ratio of USB/ALB (B/A) was calculated. The hyperbilirubinemia group was classified into three subgroups based on serum TSB levels: mild (221-256 micromol/L), moderate (257-342 micromol/L) and severe (>342 micromol/L). Serum TSB levels in the 25 normal neonates were less than 85 micromol/L (control group). NBNA was performed on the day of serum sample collection.

RESULTSSerum IGF-1 levels in the mild, moderate and severe hyperbilirubinemia groups (39.38+/- 8.42, 30.77+/- 4.65 and 26.34+/- 2.05 ng/L, respectively) were obviously lower than those in the control group (50.16+/- 15.73 ng/L) (P< 0.01). There were significant differences among the three hyperbilirubinemia subgroups in serum IGF-1 levels (P< 0.01). Mean NBNA scores in the mild, moderate and severe hyperbilirubinemia groups (35.01+/- 2.26, 32.45+/- 2.74 and 26.77+/- 5.02, respectively) were significantly lower than those in the control group (38.24+/- 0.78) (P< 0.01). Significant differences in the NBNA scores were noted among the three hyperbilirubinemia subgroups (P< 0.01). Serum IGF-1 levels were positively correlated to NBNA scores (r=0.603, P< 0.01) and negatively correlated to the ratio of B/A (r=-0.483, P< 0.01).

CONCLUSIONSSerum IGF-1 levels decreased obviously in neonates with hyperbilirubinemia and correlated to the severity of disease. IGF-1 might be associated with bilirubin-induced brain damage.

Bilirubin ; blood ; Brain ; physiology ; Female ; Humans ; Hyperbilirubinemia, Neonatal ; blood ; complications ; Infant Behavior ; Infant, Newborn ; Insulin-Like Growth Factor I ; analysis ; Male

OBJECTIVETo evaluate the effect of insulin-like growth factor 1 for the bone induction and the regulation for the fusion of the sagittal cranial sutures.

METHODSThe cells, derived from cranial sutures in the newborn SD rats and the sagittal suture from the mice, were cultured with a serum-free medium and treated with and without insulin-like growth factor 1. The osteoblast phetotypes (osteocalcin, alkaline, osteoponcin and type-1 collagen) were measured with the RT-PCR and ELISA, and the explanted sagittal sutures were then evaluated under light microscopy.

RESULTSThe cells, treated with the insulin-like growth factor 1, significantly produced more osteocalcin, alkaline, osteoponcin and type-1 collagen than those without insulin-like growth factor 1. The fusion of the sagittal suture explants will delay till to 30 days when it was not treated with IGF1. However, in the group with IGF1 the fusion was observed to start in 8 days, and a small amount of the sagittal suture fusion was found at the 20th day while a large amount was at the 30th day.

CONCLUSIONThe IGF1 has a direct effect on the fusion of cranial suture due to enhancing bone induction of cranial suture cell.

Animals ; Animals, Newborn ; Cells, Cultured ; Collagen Type I ; analysis ; Cranial Sutures ; cytology ; drug effects ; physiology ; Culture Media, Serum-Free ; Dura Mater ; Insulin-Like Growth Factor I ; pharmacology ; Mice ; Osteocalcin ; analysis ; Osteogenesis ; drug effects ; physiology ; Osteopontin ; analysis ; Rats ; Time Factors

OBJECTIVETo evaluate the potential role of insulin-like growth factor-1 receptor mRNA (IGF-IR mRNA) in the onset and development of retinopathy in diabetic rats.

METHODSA diabetic model was duplicated in Wistar rats. The early changes in the retina were examined using light and transmission electron microscopy. Expression of IGF-IR mRNA was analyzed using in situ hybridization.

RESULTSWeak expression of IGF-IR mRNA (5%) was found in retinas of normal rats, but was significantly increased (15% and 18%) in the retinas of diabetic rats after 3 and 6 months of diabetes (P < 0.01). In situ hybridization and morphological study demonstrated that there was a positive correlation between IGF-IR mRNA expression and retinal changes at various stages.

CONCLUSIONIncreased IGF-IR mRNA might play an important role in the onset and development of diabetic retinopathy.

Animals ; Blood Glucose ; analysis ; Diabetic Retinopathy ; etiology ; Glycated Hemoglobin A ; analysis ; Insulin-Like Growth Factor I ; physiology ; Male ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Receptor, IGF Type 1 ; genetics ; Retina ; metabolism ; pathology

OBJECTIVETo explore the mechanism and effect of maternal high-fat diet before and during pregnancy on bone growth of neonatal offspring rats.

METHODSForty female Sprague-Dawley rats were divided into high-fat diet and control groups (n=20) that were fed with 35% high-fat diet and standard chow, respectively. After 8 weeks, 8 female rats from each group were sacrificed for liver pathological examinations and the other female rats were mated with male rats and fed continuously with 35% high-fat diet and standard chow throughout gestation, respectively. The body lengths (from apex nasi to end of tail) of the offspring rats from both groups were measured within 24 hours after birth. Enzyme-linked immunosorbent assay was used to detect serum insulin-like growth factor (IFG-I) levels. Liver pathological changes were observed under a light microscope. The expression of insulin receptor substrate 1 (IRS-1) and phosphorylation IRS-1 (Phospho-IRS-1) in tibia and femur samples were detected by immunohistochemistry. The expression of mitogen-activated protein kinase (MAPK) and phosphorylation MAPK (Phospho-MAPK), phosphatidylinositol 3-kinase (PI3K) and phosphorylation PI3K (Phospho-PI3K), protein kinase B (AKT1) and phosphorylation AKT1 (Phospho-AKT1) in tibia and femur samples were detected by Western blot.

RESULTSThe offspring rats from the high-fat diet group showed a significant shorter body length compared with those from the control group (P<0.05). The level of serum IGF-I in offspring rats from the high-fat diet group decreased by 20.1% in comparison to those from the control group, but there was no significant difference between the two groups (P>0.05). Fatty degeneration was found in livers of both high-fat diet-fed maternal rats and their offspring rats under a light microscope. There were no significant differences in IRS-1 and Phospho-IRS-1 expression in chondrocytes of tibia and femur samples between the offspring rats of the two groups (P>0.05). The protein expression of MAPK in chondrocytes of tibia and femur samples of offspring rats from the high-fat diet group was higher than that from the control group (P<0.05). There were no significant differences of PI3K and AKT1/Phospho-AKT1 between the offspring rats of the two groups (P>0.05).

CONCLUSIONSA maternal high-fat diet before and during pregnancy may affect the bone growth of offspring rats in utero, which is possibly associated with the decreased IGF-I level. However, further study on the exact mechanism of IGF-I on the bone growth is needed.

Animals ; Bone Development ; Diet, High-Fat ; Female ; Insulin-Like Growth Factor I ; analysis ; Liver ; pathology ; MAP Kinase Signaling System ; Maternal Nutritional Physiological Phenomena ; Phosphatidylinositol 3-Kinases ; physiology ; Pregnancy ; Proto-Oncogene Proteins c-akt ; physiology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the insulin-like growth factor-I (IGF-I) gene and polypeptide expression in cultured rat osteoblast (ROB) and the role of IGF-I in mediating the cell-to-cell communication by mimicking the pharmacokinetics of parathyroid hormone (PTH).

METHODSThe ROB was cultured with three kinds of treatment: (1) Control (Ctr), the cells were cultured without PTH during the first 6 hours and the subsequent 42 hours in a 48-hour cycle; (2) Intermittent exposure to PTH (Itm), the cells were cultured with PTH during the first 6 hours, but without PTH in the subsequent 42 hours; and (3) Continuous exposure to PTH (Ctu), the cells were cultured with PTH during the first 6 hours and the subsequent 42 hours.

RESULTSThe bone-forming activities of ROB were increased in Itm and inhibited in Ctu. The IGF-I mRNA content in Itm cells was elevated only during the first 6 hours and that in Ctu cells was elevated at any time during an incubation cycle. The free IGF-I concentration in the medium of Itm cells was generally higher and that of the Ctu cells was generally lower compared with those of the Ctr cells. The IGF-I antibody significantly reduced the alkaline phosphatase activity within the cells of Ctr and Itm.

CONCLUSIONSPTH rapidly and constantly stimulates the IGF-I gene transcription of osteoblast. There was an obvious discrepancy between the IGF-I mRNA content within the osteoblast and the free IGF-I level around the osteoblast in either mode of PTH action. The IGF-I might be important for osteoblast-osteoblast communication and bone-forming activity, not only in intermittent PTH administration, but also in the physiological functioning of osteoblasts.

Animals ; Cells, Cultured ; Gene Expression ; drug effects ; Insulin-Like Growth Factor I ; genetics ; physiology ; Osteoblasts ; Parathyroid Hormone ; pharmacology ; Peptides ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Transcription, Genetic ; drug effects

This study was performed to prove the hypothesis that oncogene expressions would have the same patterns with those of cellular growth to growth factors in FRTL-5 cells. Ribonucleic acids of FRTL-5 were extracted at 15', 30', 60' and 120' after administration of growth factors to quiescent FRTL-5, and blotted to the nitrocellulose membrane. They were hybridized with radiolabelled c-fos, c-myc and beta-actin probes. Hybridized dot blots were autoradiographed and the amount of radioactivity was measured by densitometry. Densitometric readings were used as the indices of oncogene expressions. Expressions of c-fos and c-myc were more prominent in combined administrations of TSH (10 mU/ml) and IGF-I (100 ng/ml) or IgG of Graves' disease (Graves' IgG; 1 mg/ml) and IGF-I than in combined administration of TSH and Graves' IgG. IgG of primary myxedema suppressed oncogene expressions by TSH or Graves' IgG, but not by IGF-I. From the above results, it was suggested that expressions of c-fos and c-myc to growth factors would have similar patterns with those of cell growth to growth factors in FRTL-5, and the actions of TSH and Graves' IgG would be manifested through same signal transduction system, but IGF-I would be manifested by its own.
Animal ; Cell Division/drug effects/genetics ; Cell Line/cytology/physiology ; Gene Expression/drug effects/immunology ; Graves' Disease/immunology ; Growth Substances/genetics/*pharmacology ; Immunoglobulin G/pharmacology ; Insulin-Like Growth Factor I/pharmacology ; Myxedema/immunology ; Proto-Oncogene Proteins c-fos/*genetics ; Proto-Oncogene Proteins c-myc/*genetics ; RNA/analysis ; Rats ; Rats, Inbred F344 ; Support, Non-U.S. Gov't ; Thyroid Gland/cytology ; Thyrotropin/pharmacology ; Time Factors