Thyroid hormone differentially regulates rat intestinal brush border enzyme gene expression

Thyroid hormone [triiodothyronine (T₃)] has been shown to play a critical role in the growth and maturation of the mammalian small intestine, but its mechanism of action has not been well studied. In the current study, an animal model of hypothyroidism and hyperthyroidism was used to study the effects of T₃ on the small intestine. Adult rats were treated with propylthiouracil for a 6-week period and then given injections of either saline (hypothyroid) or 30 μg/100 g body wt of T₃ (hyperthyroid). Northern blot analyses showed marked differential regulation of brush border enzyme gene expression. Lactase messenger RNA (mRNA) levels decreased approximately 75% along the length of the small intestine, whereas sucrase levels were unchanged. The intestinal alkaline phosphatase mRNA species were upregulated by T₃, especially the 3-kilobase band, which increased most dramatically in jejunum. Further experiments showed significant levels of both the α-1 and β-1 T₃ receptor mRNAs within the small intestinal mucosa. Histological examination showed that T₃ treatment causes marked villus hyperplasia throughout the length of the small intestine. These results provide insight into the mechanism by which T₃ exerts its influence on the growth and differentiation of the intestinal epithelium.