Dexamethasone inhibits both growth hormone (GH)-induction of insulin-like growth factor-I (IGF-I) mRNA and GH receptor (GHR) mRNA levels in rat primary cultured hepatocytes

The aim of this study was to investigate whether glucocorticoid administration had a beneficial effect on serum concentrations of insulin-like growth factor I (IGF-I) and on IGF-binding protein 3 (IGFBP-3) in rats injected with lipopolysaccharide (LPS). Adult male rats were injected with LPS or saline and pretreated with dexamethasone or saline. Dexamethasone administration decreased growth hormone (GH) receptor and IGF-I mRNA levels in the liver of control rats. LPS decreased GH receptor and IGF-I gene expression in the liver of saline-treated rats but not in the liver of dexamethasone-pretreated rats. In the kidney, GH receptor mRNA levels were not modified by dexamethasone or LPS treatment. However, LPS decreased renal IGF-I gene expression and dexamethasone pretreatment prevented this decrease. Serum concentrations of IGF-I were decreased by LPS, and dexamethasone pretreatment attenuated this effect. The gene expression of IGFBP-3 in the liver and kidney and its circulating levels were decreased by LPS. In control rats dexamethasone increased circulating IGFBP-3 and its gene expression in the liver, and decreased the proteolysis of this protein.Dexamethasone pretreatment attenuated the LPS-induced decrease in IGFBP-3 gene expression in the liver and prevented the LPS-induced decrease in IGFBP-3 gene expression in the kidney. Moreover, dexamethasone pretreatment attenuated the LPS-induced decrease in serum concentrations of IGFBP-3 and decreased the LPSinduced IGFBP-3 proteolysis in serum. In conclusion, dexamethasone pretreatment partially attenuates the inhibitory effect of LPS on serum IGF-I by blocking the decrease of its gene expression in the kidney as well as by attenuating the decrease in serum concentrations of IGFBP-3.

Section: Discussionsupporting

confidence: 84%

Dexamethasone administration attenuates the inhibitory effect of lipopolysaccharide on IGF-I and IGF-binding protein-3 in adult rats

Priego

Granado²,

Martín³

et al. 2005

“…Our findings suggest that dexamethasone greatly increases the hepatic IGF-I response to growth hormone treatment in the neonatal period. Studies with porcine hepatocytes, too, showed increased responsiveness of IGF-I mRNA to growth hormone after dexamethasone treatment (Brameld et al 1995), but in rats dexamethasone inhibited the IGF-I response to growth hormone (Luo & Murphy 1989, Beauloye et al 1999. Because plasma insulin concentrations were elevated in the GHDX group (Hammon et al 2003), insulin might, in part, have stimulated hepatic IGF-I production, as seen in rats and cows (Böni-Schnetzler et al 1991, McGuire et al 1995.…”

Section: Discussionmentioning

confidence: 99%

The response of the hepatic insulin-like growth factor system to growth hormone and dexamethasone in calves

Hammon¹,

Zbinden²,

Sauerwein³

et al. 2003

Glucocorticoids inhibit postnatal growth and yet can stimulate the somatotropic axis around birth. The aim of the present study was to investigate the effects of dexamethasone on the somatotropic axis and on the responses of the insulin-like growth factor (IGF) system to growth hormone treatment in calves. Calves (n=24) were randomly divided into four groups. Group DX was injected with dexamethasone (30 µg/kg body weight per day), group GH was injected with 500 mg slow-release bovine growth hormone at 14-day intervals, group GHDX was injected with dexamethasone and bovine growth hormone, and group CNTRL (serving as control) was injected with saline from day 3 to day 42 of life. Blood samples were taken on day 3 and blood and liver samples were obtained on days 7, 14, 28 and 42. Body weight increased in the CNTRL and GH groups up to the end of the study and in the DX and GHDX groups up to the fourth week. Dexamethasone treatment decreased (P,0·05) plasma IGF binding protein (IGFBP)-1 on days 7 and 14, but increased (P,0·05) plasma IGFBP-1, decreased (P,0·05) plasma IGF-I and IGFBP-3, and decreased hepatic mRNA for growth hormone receptor (GHR) and IGF-I on day 42. Growth hormone treatment increased (P,0·05) plasma growth hormone concentrations on days 7 and 14, tended to increase (P,0·1) plasma IGF-I concentrations on day 42, and increased (P,0·05) hepatic mRNA levels of GHR on day 14 and IGF-I mRNA levels on days 7 and 14. The combined dexamethasone and growth hormone treatment increased plasma growth hormone concentrations on day 7 and resulted in the highest plasma concentrations of IGF-I and IGFBP-3 (day 7 to day 28) as well as the greatest abundance of hepatic GHR (day 14) and IGF-I (days 7 and 14) mRNA. Plasma IGFBP-1 concentrations in the GHDX group behaved in a similar manner as in the DX group. In conclusion, the response of the somatotropic axis to growth hormone treatment could be greatly enhanced by dexamethasone treatment during the neonatal and early postnatal period, but body weight gain was not improved. Dexamethasone alone inhibited the somatotropic axis and postnatal growth after the first month of life.

“…Primary hepatocyte culture studies in mammals and birds have shown that pancreatic, stress and thyroid hormones can both regulate IGF-I production independently of GH, and modulate the effect of GH on IGF-I production. Insulin, thyroid hormones and low concentrations of glucocorticoids potentiate GH-stimulated IGF-I mRNA expression, whereas glucagon and high concentrations of glucocorticoids inhibit basal or GH-stimulated IGF-I expression (Tollet et al 1990, Boni-Schnetzler et al 1991, Houston & O'Neill 1991, Denver & Nicoll 1994, Brameld et al 1995, Beauloye et al 1999. In vivo data support a physiologically significant positive role for insulin in the regulation of GH sensitivity (Griffen et al 1987).…”

Section: Introductionmentioning

confidence: 85%

Metabolic hormones modulate the effect of growth hormone (GH) on insulin-like growth factor-I (IGF-I) mRNA level in primary culture of salmon hepatocytes

Pierce

Fukada²,

Dickhoff³

2005

Liver production of insulin-like growth factor-I (IGF-I) is a major point of control in the growth hormone (GH)/IGF axis, the endocrine system regulating body growth in fishes and other vertebrates. Pituitary GH stimulates hepatocyte production of IGF-I; however, in catabolic states, hepatocyte GH resistance results in decreases in liver IGF-I production. To investigate endocrine mechanisms leading to the development of hepatocyte GH resistance, we examined the regulation of IGF-I mRNA level by GH and metabolic hormones in primary culture of salmon hepatocytes. Cells were cultured in RPMI medium, and exposed to insulin (Ins, 10 6