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Thyroid hormone responsiveness is developmentally regulated in the rat small intestine: a possible role for the
R A Hodin1, S Meng, S M Chamberlain
1Department of Surgery, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215.
Abstract:
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.
Insights
Thyroid hormone (T3) responsiveness in the developing rat small intestine increases with age. This change correlates with a decrease in the inhibitory T3 receptor variant, c-erbA alpha-2.
Area of Science:
- Endocrinology
- Molecular Biology
- Developmental Biology
Background:
- Thyroid hormone (T3) regulates gene expression via nuclear receptors (TRs).
- TRs are encoded by alpha and beta c-erbA genes, with TR beta-1 being major in adult rat intestine.
- c-erbA alpha-2, a non-hormone-binding variant, is present and may inhibit T3 action.
Purpose of the Study:
- To investigate the developmental regulation of T3-responsive genes (lactase and intestinal alkaline phosphatase [IAP]) in the rat small intestine.
- To examine the expression of T3 receptor variants (TR beta-1 and c-erbA alpha-2) during postnatal development.
Main Methods:
- Developing rats (10 and 25 days old) were treated with T3 or saline.
- Northern blot analysis was used to quantify lactase and IAP mRNA levels in jejunal tissues.
- TR beta-1 and c-erbA alpha-2 mRNA levels were also assessed via Northern analysis.
Main Results:
- T3-induced changes in lactase and IAP gene expression were significantly greater in 25-day-old rats compared to 10-day-old rats.
- Jejunal IAP mRNA increased 15-fold with T3 treatment at 25 days, while lactase mRNA decreased by 75%.
- TR beta-1 mRNA levels remained constant, but c-erbA alpha-2 mRNA levels decreased by 90% between 5 and 25 days.
Conclusions:
- The rat small intestine exhibits increasing T3 responsiveness during postnatal development.
- The decline in c-erbA alpha-2 expression parallels the increased T3 responsiveness, suggesting its inhibitory role.
- These findings highlight the developmental interplay between T3 receptor variants and target gene regulation.