Glucocorticoids are not necessary for the inhibitory effect of endotoxic shock on serum IGF-I and hepatic IGF-I mRNA

Abstract

The aim of this work was to elucidate the possible role of glucocorticoids in the bacterial lipopolysaccharide (LPS)-induced decrease in hepatic IGF-I synthesis. For this purpose, we studied the effect of LPS on IGF-I in two rat strains, Wistar and Lewis, which have different adrenal responses to inflammation. Compared with Wistar rats, Lewis rats have a reduced hypothalamic-pituitary-adrenal response to inflammatory stimuli. Rats received two i.p. injections of 1 mg/kg LPS and were killed 4 h after the second injection. LPS induced an increase in serum concentrations of both ACTH and corticosterone, the increase being more pronounced in Wistar than in Lewis rats. LPS decreased hepatic GH receptor (GHR) and IGF-I mRNA only in Wistar rats. However, serum concentrations of IGF-I were significantly decreased (P<0·01) in both Wistar and Lewis rats. These data indicate that the adrenal axis may mediate the inhibitory effect of LPS on GHR and IGF-I synthesis in the liver. In a second experiment, adrenalectomized or sham-operated Wistar rats were injected with LPS. Two LPS injections (0·1 mg/kg) decreased serum concentrations of IGF-I in both type of rat; however, the inhibitory effect of LPS on liver GHR and IGF-I mRNA was observed in adrenalectomized rats, but not in intact rats. All these data suggest that some component of the adrenal axis, other than glucocorticoids, mediates the inhibitory effect of LPS on liver GHR and IGF-I.

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

“…As previously reported, LPS injections decreased GH receptor and IGF-I mRNAs in the liver (Priego et al 2002a(Priego et al , 2003a. However, in the kidney, LPS did not affect GH receptor gene expression, although it decreased IGF-I gene expression, as in the liver.…”

“…In these conditions, we found that LPS decreased IGF-I gene expression in the kidney. Furthermore, in chronic inflammation we also found a decrease in renal IGF-I mRNA (Ibáñez de Cáceres et al 2002a).…”

“…However, we have recently reported that glucocorticoids are not responsible for the inhibitory effect of LPS on circulating IGF-I and IGFBP-3, as well as their gene expression in the liver (Priego et al 2002a,b). Moreover, prevention of the increase in glucocorticoid secretion after LPS by adrenalectomy potentiates the inhibitory effect of LPS on serum and liver IGF-I (Priego et al 2002a). This fact suggests that glucocorticoids have a beneficial effect, probably preventing the release of an IGF-I inhibitory factor.…”

“…LPS administration decreases circulating levels of IGF-I both in humans and in experimental animals (Fan et al 1994, Soto et al 1998. We have previously observed that the decrease in serum IGF-I is associated with a decrease in growth hormone (GH) receptor and IGF-I synthesis in the liver (Priego et al 2002a(Priego et al , 2003a.…”

“…LPS administration to rats induces an activation of the hypothalamic-pituitary-adrenal axis, shown by an increase in serum adrenocorticotropin and corticosterone concentrations (Fan et al 1994, Priego et al 2002a. The increased levels of glucocorticoids after acute endotoxin exposure could be the mediator of depressed serum and liver IGF-I levels, since the glucocorticoid, dexamethasone, inhibits IGF-I synthesis in the liver (Luo & Murphy 1989) and decreases GH receptor (Gabrielsson et al 1995).…”