Effects of Hypothyroidism on Jejunal Mucosal Function: Study by In Situ Luminal Perfusion in Rats

ABSTRACT: To assess the effects of hypothyroidism (HT) on small-intestinal function, HT was induced in rats (120–150 g) by methimazole in drinking water. After 6 wk of methimazole, intestinal absorption studies were performed in HT and in control (C) rats by in situ luminal perfusion of a 20-cm proximal jejunal loop with a bicarbonate buffer containing sodium, glucose or fructose, glycine or lysine, and phenol red as a nonabsorbable marker for determination of water fluxes. Mucosa from the perfused segment was taken for assay of disaccharidases and ATPases and for light and electron microscopy. Compared with C rats, HT rats had significantly lower jejunal transport rates of water (2.54 ± 0.36 versus 5.02 ± 0.7 μL/min/μg mucosal protein, p < 0.03), sodium (37.1 ± 10.3 versus 102.7 ± 18.6 μmol/min/μg protein, p < 0.05), and glucose (1.49 ± 0.28 versus 5.17 ± 0.82 μmol/min/μg protein, p < 0.02). A reduction in glycine transport was also observed but did not attain statistical significance (p = 0.058). Fructose and lysine transport was unchanged. Mucosal sucrase and Iactase activities were similar in both groups, but Na,K-ATPase was significantly lower in HT rats (1.17 ± 0.3 versus 4.03 ±1.5 μmol inorganic phosphate/h/mg protein; p < 0.05), with a diminution of ouabain binding sites by 41.5%. Light microscopy of jejunal mucosa from HT rats did not differ from that from C rats; electron microscopy showed mild mitochondrial swelling in HT enterocytes. A group of HT rats were treated with L-thyroxine during 4 wk; these rats had absorption rates, mucosal enzyme activities, ouabain binding, and mucosal morphology not different from C rats. We conclude that HT in the rat can depress jejunal mucosal Na,K-ATPase activity and reduce Na,K-ATPase-dependent transport without structural changes other than mild enterocyte mitochondrial swelling. A diminished jejunal functional capacity might add a nutritional component to the growth retardation that is observed in HT.