Ontogeny of intestinal lactase: posttranslational regulation by thyroxine.
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.
Liu
T
T
Department of Pediatrics, Stanford University, California 94305.
Reisenauer
A M
AM
Castillo
R O
RO
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism*; D002465:Cell Movement; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006207:Half-Life; D007037:Hypothyroidism / Q000201:enzymology; D007422:Intestines / Q000166:cytology / Q000201:enzymology*; D043322:Lactase; D011247:Pregnancy; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013974:Thyroxine / Q000502:physiology*; D014018:Tissue Distribution; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*
D043322:Lactase; D001616:beta-Galactosidase; D013974:Thyroxine