Cortisol increases GH receptor expression
High levels of glucocorticoids are well known to cause osteoporosis, and physiological levels of growth hormone (GH) are required for a normal bone remodeling. It has been suggested that glucocorticoids regulate the GH-response via a regulation of GH-receptor expression. The aim of the present study was to investigate whether or not cortisol regulates growth hormone receptor expression in cultured human osteoblasts.
The effect of serum starvation and cortisol on GH-receptor expression was tested in human osteoblast-like cells. Serum starvation for 24h resulted in an increase in GH-receptor mRNA levels (90±1% over control culture). Cortisol increased GH-receptor mRNA levels in a dose-dependent manner with a maximal effect at 10-6 M. The stimulatory effect of cortisol on GH-receptor mRNA levels was time dependent, reaching a peak after 12 h (126±29% over control culture) and the effect was still present 12 h later. The increase in GH-receptor mRNA levels was accompanied by an increase in 125I-GH binding with a maximal effect at 24 h (196±87% over control culture).
In conclusion, glucocorticoids increase GH-receptor expression in human osteoblast-like cells. Further studies are needed to clarify whether or not a glucocorticoid-induced regulation of the GH- receptor is of importance to human bone physiology.
Dual mode of cortisol action on GH/IGF-1/IGFBP's
Glucocorticoids are known to impede somatic growth in a wide range of vertebrates. In order to clarify the mechanisms through which they may act in an advanced teleost fish, we examined the effects of cortisol administration on the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF-binding protein (IGFBP) system in the tilapia (Oreochromis mossambicus). In a short-term experiment, fish were injected intraperitoneally with cortisol (2 or 10 mg/g), and sacrificed at 2, 4, 8 and 24 h after the injection. In a longer-term experiment, fish were sacrificed 24 and 48 h after cortisol injection (2, 10 and 50 mg/g). Cortisol at doses of 2 and 10 mg/g increased four different sizes of IGFBPs (24, 28, 30, and 32 kDa) significantly in the plasma within 2 h without altering the plasma levels of IGF-I or GH. On the other hand, cortisol at doses of 10 and 50 mg/g significantly reduced plasma IGF-I levels after 24 and 48 h. IGF-I mRNA levels in the liver were also significantly reduced by cortisol at doses of 10 and 50 mg/g after 48 h, suggesting that a decrease in plasma IGF-I levels is mediated through the attenuation of IGF-I gene expression in the liver. In contrast, no significant change was observed in plasma or pituitary contents of GH at any time point examined, which would appear to indicates that cortisol reduces IGF sensitivity to GH (GH- resistance). These results clearly indicate that cortisol induces a rapid increase in plasma IGFBPs and a more delayed decrease in IGF-I production. The dual mode of cortisol action may contribute to the inhibitory influence of cortisol on somatic growth in teleosts.