Hormonal regulation of adaptive intestinal growth in artificially reared rat pups

Adaptive growth and precocious expression of sucrase activity occur in the small intestine of artificially reared (AR) rat pups fed a hormone-free diet. The physiological mechanisms underlying adaptive intestinal growth were studied. Day 12 rat pups that received jejunal isografts subcutaneously on day 0 were subjected to artificial feeding and were killed on day 16. Crypt cellularity and DNA labeling index in isografts from AR, but not from mother-fed, rats increased significantly to levels found in in situ host jejunum of AR rats, indicating that humoral regulatory mechanisms are responsible for intestinal cell proliferation in AR pups. Radioimmunoassays of serum corticosterone, thyroxine, insulin, and gastrin and of gastric gastrin contents revealed that only serum corticosterone concentrations were significantly elevated, suggesting that corticosterone plays a critical role for intestinal growth. To examine this possibility directly, day 12 rats were adrenalectomized (ADX) and AR by continuous infusion of diets containing 0, 10, or 50 micrograms/ml corticosterone. Serum corticosterone concentrations paralleled the infused doses of corticosterone. Jejunal DNA labeling index increased in all ADX AR rats at day 13 in a dose-dependent manner. Increased jejunal DNA labeling index was maintained on day 14 in intact AR rats and ADX AR rats fed 10 micrograms/ml corticosterone but not in ADX AR rats receiving 0 or 50 micrograms/ml. We conclude that endogenous corticosterone is one of the systemic factors responsible for the adaptive increase in intestinal growth of AR rats.