Thyroxine and cortisone cooperate to modulate postnatal intestinal enzyme differentiation in the rat

Interactions of cortisone and thyroxine (T4) in modulating jejunal sucrase and lactase expression were studied in rats during early postnatal life. Cortisone (50 micrograms/g body wt) precociously induced sucrase activity in days 5-16 rats and enhanced activity thereafter until day 22. T4 (1 microgram/g) plus cortisone evoked greater sucrase expression in day 9 or younger rats. T4 did not induce sucrase expression until day 13. Lactase activity was enhanced in rats younger than day 9 by cortisone, and this effect was abolished when T4 was added. In days 19 and 22 rats, cortisone depressed lactase; with T4, lactase activity was further decreased. T4 alone did not suppress lactase activity until day 19. Quantitation of jejunal enzyme content showed that sucrase catalytic activity was higher in day 22 than 19 or younger rats and lower in rats given T4 than cortisone. In contrast, lactase activity remained constant in all animal groups. In vivo [35S]methionine-labeling studies using day 9 rats showed that cortisone induced de novo synthesis of sucrase and increased 35S incorporation into lactase. Cortisone plus T4 increased 35S incorporation into sucrase further and significantly increased 35S incorporation into lactase. We conclude that 1) cortisone and T4 cooperatively stimulate sucrase expression and reduce lactase activity during early postnatal life and 2) reduction in lactase activity accompanied by increase in lactase synthesis suggests that cortisone and T4 regulate lactase activity at posttranslational level.