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The residual small bowel undergoes profound adaptive alterations after surgical resection. GH is considered to have a role in regulation of these adaptive changes, but its precise role is unknown. We investigated the role of GH by studying the response to intestinal resection in rats with isolated GH deficiency. Spontaneous dwarf rats, a strain of rats with congenital isolated GH deficiency, underwent 60% resection of the small intestine and parameters of the response of the intestinal remnant were compared with age-matched GH-deficient rats undergoing transection, GH-normal rats undergoing 60% resection, and nonmanipulated GH-normal rats. Deficiency of GH did not inhibit hyperplasia of the mucosal mass of the intestinal remnant, indicating that GH is not required for regulation of this aspect of the adaptive response. However, GH deficiency resulted in lack of accumulation of mucosal protein, including lack of accumulation of digestive hydrolases. In addition, GH deficiency resulted in alterations in processing of digestive hydrolases of the distal intestine, indicating that GH may have region-specific effects on small intestinal function. We conclude that GH is required for the normal expression of specific components of the adaptive response to massive small intestinal resection, but not for all aspects. The aspects that require GH appear to involve protein synthesis and processing.

During the 3rd wk of postnatal life in the rat, dramatic maturational changes occur in the structure and function of the small intestine, enabling the animal to make the transition from milk to solid food. To investigate the role of GH in the regulation of this complex process, we studied postnatal intestinal maturation in the spontaneous dwarf rat, a strain of Sprague-Dawley rats with an autosomal recessive mutation in the GH gene resulting in complete but isolated GH deficiency. GH-deficient and GH-normal littermates were studied at d 7 and 14 (suckling) and d 23 (postweaned). The body weight of GH-deficient animals was inhibited by 60% at each age. Longitudinal growth of the small intestine was not inhibited, suggesting that longitudinal small bowel growth is independent of GH regulation. Mucosal cell mass was significantly lower in GH deficiency at all ages studied, and digestive hydrolase capacity per cm of intestine was significantly lower in GH-deficient postweaned animals. However, epithelial cell mass increased markedly in association with weaning and the maturation of lactase, sucrase, and aminooligopeptidase proceeded normally in GH deficiency. These data suggest that, although GH is not required for normal postnatal intestinal maturation, the mucosal epithelial hypoplasia found in GH-deficient animals suggests that GH or GH-dependent factors act as an intestinal mucosal growth factor whose function is to promote the homeostatic or steady-state regulation of mucosal epithelial growth.

IGF binding proteins (IGFBP) regulate the bioavailability and bioactivity of IGF. The major IGFBP in serum is IGFBP-3. We investigated whether sera from children with malignancies show alterations in levels of IGFBP-3 as measured by Western ligand blot analysis (WLB) and RIA with alpha IGFBP-3gl, a specific rabbit polyclonal antibody. Furthermore, IGFBP-3 proteolysis was quantified by densitometric analysis of [125I]IGFBP-3 protease assays, and IGFBP-3 fragments were visualized by Western immunoblot with alpha IGFBP-3gl. We examined sera from 21 children with solid tumors, five patients with sarcoma who had reached complete remission, and 13 children with acute leukemia. Serum samples were collected at diagnosis, before initiation of therapy. Sera of 10 healthy children served as normal controls. Children with solid tumor or leukemia had significantly higher (p < 0.001) IGFBP-3 protease activity in serum than did normal controls or patients with sarcoma in complete remission. Corresponding to this finding, densitometry of WLB showed lower IGFBP-3 levels in sera of children with malignancies in comparison with normal controls. The negative correlation (p < 0.001, r = -0.80) between IGFBP-3 proteolysis, as measured by [125I]IGFBP-3 protease assay, and IGFBP-3 band density on WLB indicates that proteolysis is the probable reason for reduction of IGFBP-3 on WLB. IGFBP-3 concentrations measured by RIA were in the normal range for most patients, further indicating that differences in serum IGFBP-3 levels measured by WLB reflect protease activity.(ABSTRACT TRUNCATED AT 250 WORDS)