Thyroid hormone responsiveness is developmentally regulated in the rat small intestine: a possible role for the alpha-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 alpha and beta c-erbA genes. We have previously found that TR beta-1 is the major receptor form expressed in the adult rat small intestine, although there are also moderate levels of c-erbA alpha-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 micrograms/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 beta-1 mRNA levels were unchanged during the developmental period, whereas the levels of c-erbA alpha-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 alpha-2 levels, suggesting that this T3 receptor variant may play a role in this hormonal responsiveness.
Department of Surgery, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215.
R A
RA
Hodin
S
S
Meng
S M
SM
Chamberlain
D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D014644:Genetic Variation; D007421:Intestine, Small / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism; D043322:Lactase; D008871:Microvilli / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000502:physiology*; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology*; D014886:Weaning; D001616:beta-Galactosidase / Q000235:genetics
D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D000469:Alkaline Phosphatase; D043322:Lactase; D001616:beta-Galactosidase