ROLE OF GI-I AND IGF-I IN THE REGULATION OF IGF-I, IGF-I RECEPTOR ANDIGF BINDING-PROTEIN GENE-EXPRESSION IN THE RAT SPLEEN

To characterize the expression of the IGF-I system in the spleen and i ts 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 s everal 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 mu g/animal/day), or recombinant human IGF-I (rhIGF-I; 125 mu g/anima l/day) for 11 days. Compared to sham-operated controls, Hx animals exh ibited 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 i n Hx animals was partially prevented by both bGH and rhIGF-I. Body wei ghts 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 mainta ined IGF-I levels. Hypophysectomy reduced spleen IGF-I mRNA levels (30 .6 +/- 7.5 % of control values; P < 0.05) and this reduction was preve nted by bcH (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 pro tein (IGFBP) mRNA levels were studied under these conditions, we found that IGFBP-1 mRNA was not detected in spleen; IGFBP-2 mRNA levels wer e reduced in Hx rats (67.9 +/- 7.4% of control values, P < 0.05) and b GH treatment prevented this reduction (95.5 +/- 12.2%,, NS). IGFBP-3 m RNA levels were not affected by hypophysectomy or by bGH treatment, bu t 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 in crease. These data demonstrate that several components of the IGF syst em are expressed in rat spleen and that following hypophysectomy, ther e is a reduction in spleen weight that correlates with a reduction in local IGF-I gene expression and, presumably, a reduction in IGF-I bioa vailability due to a decrease in IGFBP-2 and an increase in IGFBP-4 ge ne expression.