AJP - Gastrointestinal and Liver Physiology, Vol 263, Issue 4 538-G543, Copyright © 1992 by American Physiological Society
Ontogeny of intestinal lactase: posttranslational regulation by thyroxine
T. Liu, A. M. Reisenauer and R. O. Castillo
Department of Pediatrics, Stanford University, California 94305.
To assess the molecular mechanisms underlying the regulation of lactase
ontogeny by thyroxine (T4), we performed an in vivo study of lactase
catalytic activity, synthesis, subunit structure, degradation, and
enterocyte migration rates in propylthiouracil-induced hypothyroid rat
pups, hypothyroid pups injected with T4, and normally weaned rats. Although
lactase catalytic activity remained elevated in the hypothyroid rats and
declined normally in the other two groups, lactase synthesis was constant
among the groups. Lactase subunit structure was identical in normally
weaned and T4-injected animals, but the 100-kDa moiety, characteristic of
weaned rats, was absent in the hypothyroid pups. The turnover of lactase
enzyme was more rapid in euthyroid and T4-injected rats than in hypothyroid
animals (t1/2 = 17, 20, and 30 h, respectively). In addition, enterocyte
migration was accelerated in the T4-injected rats and reduced in the
hypothyroid group compared with controls. However, transit rate was not
directly related to lactase activity. Our results suggest that T4 regulates
lactase ontogeny by posttranslational mechanisms that include altered
processing and increased degradation of the lactase enzyme.
