GROWTH-HORMONE (GH) REGULATION OF SUBMANDIBULAR-GLAND STRUCTURE AND FUNCTION IN THE CH-DEFICIENT RAT - UP-REGULATION OF HAPTOCORRIN

Based on localization studies of the GH receptor/binding protein (BP) in the gastrointestinal tract, we have recently demonstrated growth ho rmone regulation of gastric intrinsic factor. In order to define the r ole of GH in the submandibular gland (SMG) we have investigated the ef fect of GH on SMG structure and function with particular reference to haptocorrin. Bovine GH (65 mu g/100 g body weight) was administered tw ice daily to adult male dwarf rats for 6 days (DW+) while control anim als received vehicle (DW-). Administration of GH produced a significan t increase in body weight (P<0.001) and an allometric increase in SMG weight (P=0). There was no change in RNA or protein content per g SMG and GH administration produced a small decrease in DNA content normali zed to SMG weight. Morphometric analysis of the SMG revealed a signifi cant increase in the percentage area of the gland occupied by tubular (GH receptor/BP expressing) structures and a significant increase in t he diameter of both the intralobular striated and granular convoluted tubules. The effect of GH on cellular proliferation in the ductular an d acinar components was determined by the immunohistochemical detectio n of nuclear 5'-bromo-2'-deoxyuridine (BrdU) incorporated during a 2-h pulse of BrdU. GH treatment induced a 5.5-fold increase in the labell ing index of tubular cells whereas the acinar cell labelling index inc reased only 3.3-fold. Soluble extracts of SMG were prepared for estima tion of Co-57-cyanocobalamin (vitamin B12) binding. GH administration resulted in an increase in total Co-57-cyanocobalamin (CBL) binding pe r mg SMG protein. To determine the contribution of haptocorrin (R-prot ein) the amount of cobinamide dicyanide (CD) displaceable binding was calculated. GH administration produced a 70% increase in CD displaceab le CBL binding per mg SMG indicating GH regulation of haptocorrin. A c omparison of total SMG CBL binding and CD displaceable CBL binding bet ween male and female rats detected no sex difference. Therefore sex-sp ecific GH secretory profiles are unlikely to be of importance in the r egulation of haptocorrin. In conclusion we have demonstrated that GH s timulates hypertrophy and hyperplasia of components of the SMG in the dwarf rat. The observed upregulation of haptocorrin may synergize with the GH-stimulated increase in intrinsic factor to facilitate absorpti on of CBL during the anabolic state.