Thyroid hormone responsiveness is developmentally regulated in the rat small intestine: A possible role for the α-2 receptor variant

Thyroid hormone (T₃) alters gene expression through binding to a receptor protein located within the nucleus of target cells. Multiple forms of the T₃ receptor (TR) have been identified and are encoded by the α and β c-erbA genes. We have previously found that TR β-1 is the major receptor form expressed in the adult rat small intestine, although there are also moderate levels of c-erbA α-2, a nonhormone-binding variant that is thought to inhibit T₃ action. In developing rats, we studied the regulation of two small intestinal enterocyte genes previously shown to be T₃ responsive, lactase and 3.0-kilobase intestinal alkaline phosphatase (IAP). Animals were treated with six daily ip injections of either saline (control) or 30 μgrams/100 g BW T₃ (T₃ group) and killed at 10 and 25 days of age. Northern analyses of RNA derived from intestinal tissues showed that the magnitude of the T₃-induced changes in lactase and IAP gene expression increased with development. Jejunal 3.0-kilobase IAP messenger RNA (mRNA) levels were unaffected by T₃ at 10 days, but increased by 15-fold at 25 days. Similarly, jejunal lactase mRNA levels were unchanged by T₃ at 10 days, but decreased by 75% at 25 days. Qualitatively similar results were seen in the duodenum and ileum. Studies of TR expression revealed that TR β-1 mRNA levels were unchanged during the developmental period, whereas the levels of c-erbA α-2 decreased by 90% between 5-25 days after birth. These results indicate that the rat small intestine becomes increasingly T₃ responsive during postnatal development. These changes occur in parallel with a decline in c-erbA α-2 levels, suggesting that this T₃ receptor variant may play a role in this hormonal responsiveness.