Role of GH and IGF-I in the regulation of IGF-I, IGF-I receptor and IGF binding protein gene expression in the rat spleen

To characterize the expression of the IGF-I system in the spleen and its role in spleen growth, we have studied the effect of hypophysectomy and the action of either GH or IGF-I treatment on the expression of several components of the IGF system in the rat. Female Sprague-Dawley rats were hypophysectomized (Hx) on postnatal day 50, and five animals each received twice-daily sc injections of saline, bovine GH (bGH; 84 μg/animal/day), or recombinant human IGF-I (rhIGF-I; 125 μg/animal/day) for 11 days. Compared to sham-operated controls, Hx animals exhibited a reduction in both body (192.6 ± 5.6 g (mean ± S.E.M.) vs. 268.6 ± 6.0 g; P<0.001) and spleen weights (0.42 ± 0.03 g vs. 0.84 ± 0.06 g; P<0.001). The reduction in body and spleen weights in Hx animals was partially prevented by both bGH and rhIGF-I. Body weights were 234.2 ± 5.3 g (P<0.001) after bGH and 213.8 ± 6.3 g (P<0.05) after rhIGF-I. Spleen weights were 0.56 ± 0.048 after bGH P<0.01 and 0.53 ± 0.05 g after rhIGF-I (P<0.05). Serum GH and IGF-I levels were markedly reduced in Hx animals and bGH partially maintained IGF-I levels. Hypophysectomy reduced spleen IGF-I mRNA levels (30.6 ± 7.5% of control values; P<0.05) and this reduction was prevented by bGH (96.6 ± 24.2%; NS) but not by rhIGF-I (39.9 ± 5.0% NS vs. Hx). There were no changes in GH receptor or IGF-I receptor mRNA levels in Hx or bGH or rhIGF-I-treated animals. When IGF-I binding protein (IGFBP) mRNA levels were studied under these conditions, we found that IGFBP-1 mRNA was not detected in spleen; IGFBP-2 mRNA levels were reduced in Hx rats (67.9 ± 7.4% of control values, P<0.05) and bGH treatment prevented this reduction (95.5 ± 12.2%, NS). IGFBP-3 mRNA levels were not affected by hypophysectomy or by bGH treatment, but were reduced in rhIGF-treated rats (69.6 ± 3.0%, P<0.05). On the other hand, IGFBP-4 mRNA levels were increased in Hx rats (136.4 ± 15.9% of control values, P<0.05) and bGH treatment prevented this increase. These data demonstrate that several components of the IGF system are expressed in rat spleen and that following hypophysectomy, there is a reduction in spleen weight that correlates with a reduction in local IGF-I gene expression and, presumably, a reduction in IGF-I bioavailability due to a decrease in IGFBP-2 and an increase in IGFBP-4 gene expression.