Growth factor-I Gene Expression Research Articles

Effects of Insulin and Insulin-like Growth Factor-I on Renin Gene Expression in the Renal Cortical Cells of Ovine Fetuses

Renin gene expression and insulin-like growth factor-I (IGFI) gene expression are both developmentally upregulated in the renal cortex of ovine fetuses and decline after birth. The infusion of IGFI into ovine fetuses in late gestation increases plasma renin activity and concentration. In order to determine whether there are direct effects of IGFI or insulin on renin gene expression in the kidneys of ovine fetuses, we treated the renal cortical cells of ovine fetuses with IGFI or insulin. The results showed that the responses of renal renin mRNA to IGFI or insulin treatment in vitro were dependent on the culture conditions. Renin mRNA levels were significantly elevated by IGFI or insulin if the cells were cultured in medium devoid of serum (starved) for 16-18 h before treatment. In contrast, no obvious changes in renal renin mRNA expression were observed in the cells cultured in the presence of serum (non starved) before treatment with IGFI or insulin. IGFI and insulin also significantly enhanced cAMP concentrations in the medium of the cells starved in vitro. The data suggest that IGFI and insulin can act directly on the renal cortical cells from ovine fetuses to stimulate renin mRNA expression. It is possible that IGFI and insulin stimulate renin mRNA expression by increasing cAMP concentration in the cells.

Refeeding increases hepatic insulin-like growth factor-I (IGF-I) gene expression and plasma IGF-I concentration in fasted chicks

1. We examined the influence of refeeding after 2 d of fasting on plasma insulin-like growth factor-I (IGF-I) concentration and hepatic IGF-I gene expression in chickens at 6 weeks of age. 2. Hepatic IGF-I mRNA was measured by ribonuclease protection assay and plasma IGF-I concentration was determined by radioimmunoassay. 3. Plasma IGF-I concentration decreased following fasting, increased to the level of fed controls after 2 h of refeeding but then fell back to the level of fasted chickens after 6 h of refeeding. 4. Fasting reduced hepatic IGF-I mRNA concentrations to less than half of those in the fed controls. Refeeding increased IGF-I mRNA sharply at 2 h after refeeding, but by 6 h after refeeding they had taller back again to levels significantly lower than at 2 h. 5. A significant correlation between plasma IGF-I concentration and hepatic IGF-I gene expression was found, suggesting that when chicks are refed after 2 d of fasting, the short-term increase in plasma IGF-I concentration may be partly regulated by the alteration in hepatic IGF-I mRNA.

Relationship of Insulin-Like Growth Factor-I to Muscle Protein Synthesis in Fasted Chicks.

The influence of 1 day fasting on muscle protein synthesis, hepatic insulin like growth factor-I (IGF-I) gene expression and plasma IGF-I concentration was investigated in chicks at 1 and 2 weeks of age. The fractional synthesis rate (Ks) of breast muscle protein was measured by a large dose injection of L-[2, 6-3 H] phenylalanine (Experiment 1). Hepatic IGF- I mRNA was measured by ribonuclease protection assay (Experiment 1) and plasma IGF-I concentration was determined by radioimmunoassay (Experiment 2). The Ks value for muscle protein was significantly decreased from 1 to 2 weeks of age. Fasting significantly decreased Ks and the amount of protein synthesized. The relative intensity of bands of the protected IGF- I mRNA fragment tended to increase, but not significantly, from 1 to 2 weeks of age. Whereas hepatic IGF-I mRNA levels were significantly reduced by fasting. Plasma IGF-I concentration significantly increased from 1 to 2 weeks of age. There was a significant reduction in plasma IGF-I level of fasted chicks. The relative intensity of hepatic IGF-I mRNA bands was significantly related to the amount of muscle protein synthesized. These results suggest that the influence of fasting and age on muscle protein synthesis in the chicken during early stages of posthatching growth may be, at least partially, regulated by changes in plasma IGF-I level resulted from alterations in hepatic IGF-I gene expression.

The ontogeny of hepatic growth hormone receptor and insulin-like growth factor I gene expression in the sheep fetus during late gestation: developmental regulation by cortisol.

The effects of cortisol on hepatic GH receptor and insulin-like growth factor-I (IGF-I) gene expression were investigated in sheep fetuses during late gestation and after experimental manipulation of plasma cortisol levels by fetal adrenalectomy and exogenous infusion of cortisol. Hepatic GH receptor and IGF-I messenger RNA (mRNA) levels increased with increasing gestational age in parallel with the normal rise in fetal cortisol levels toward term (145 +/- 2 days). These increases in mRNA abundance toward term were prevented when the prepartum cortisol surge was abolished by fetal adrenalectomy and were stimulated prematurely in fetuses younger than 130 days by exogenous infusion of cortisol. Both the class 1 and class 2 transcripts of the IGF-I gene were increased when cortisol levels were elevated either endogenously or exogenously. However, there were no significant changes in fetal plasma IGF-I levels either with increasing gestational age or in response to experimental manipulation of the fetal cortisol level. When the data from all the fetuses were combined irrespective of treatment or gestational age, there were significant positive correlations between the log plasma cortisol concentration in utero and the abundance of GH receptor and IGF-I mRNA in the fetal liver. There was also a significant inverse relationship between log plasma cortisol and the ratio of class 1 to class 2 transcript abundance in the fetal liver. These findings show that cortisol is a physiological regulator of hepatic GH receptor and IGF-I gene expression in fetal sheep during late gestation and indicate that it preferentially increases the class 2 transcript of the IGF-I gene. The prepartum cortisol surge therefore appears to have an important maturational role in initiating the perinatal switch from the fetal to adult modes of somatotrophic regulation.

Effect of testosterone on insulin-like growth factor-I (IGF-I) and IGF-I receptor gene expression in the hypophysectomized rat.

Circulating levels of insulin-like growth factor-I (IGF-I) increase during puberty, concurrent with an increase in the levels of GH and the gonadal steroids. The relationship between the changes observed in IGF-I and testosterone (T) levels are not understood. This study was designed to determine whether T has a direct effect on IGF-I serum levels, liver IGF-I gene expression, and epiphyseal growth plate IGF-I and IGF-I receptor gene expression. Hypophysectomized castrated rats were divided into four groups of six animals. The T group was treated with sc T for 5 days. The GH group was treated with a single dose of GH. The GH plus T group was treated with T for 5 days and with GH on the last day of treatment. The control group was injected for 5 days with vehicle alone. Serum IGF-I levels in the T group were not significantly different from those in the control group, and the levels in the GH plus T group were not significantly different from those in the GH group. There was an 11-fold increase in liver IGF-I mRNA abundance in the GH group compared to the control group (P less than 0.01). Liver IGF-I mRNA levels in the T group were not significantly different from those in the control group. When liver IGF-I mRNA levels in the GH plus T group were compared to those in the GH-treated group, no significant differences were found. In the epiphyseal growth plate region, there was a 12-fold increase in IGF-I mRNA levels in the GH group compared to those in the control group, but there was no statistical difference between the control and T groups. IGF-I mRNA levels in the GH plus T group were not significantly different from those in the GH-treated group. IGF-I receptor mRNA abundance was not significantly different in the T group compared to that in the control group. GH decreased IGF-I receptor mRNA by 2.3-fold, but T treatment before GH injection did not change this effect. We conclude that in castrated hypophysectomized rats, T does not stimulate IGF-I gene expression in the liver, nor does it increase IGF-I serum levels. T alone also does not have a stimulatory effect on IGF-I or IGF-I receptor gene expression in the epiphyseal growth plate region.(ABSTRACT TRUNCATED AT 400 WORDS)