Mosaic regulation of lactase in human adult-type hypolactasia.

Abstract

We have previously shown that in the proximal-jejunum of hypolactasic humans, just a few villus enterocytes express lactase protein and activity. In the present study, we compared the distribution of lactase messenger RNA (mRNA), protein, and activity in villus enterocytes in tissues obtained from subjects with persistent high lactase activity and those with hypolactasia. Immunohistochemical and enzymohistochemical staining was performed on closely adjacent sections of human proximal jejunum from 5 individuals with persistent high lactase activity and 32 with hypolactasia. In all the persistent and in 9 hypolactasic samples, in situ hybridization was also performed using a digoxygenin-labeled RNA probe. In persistent tissues, lactase mRNA, protein, and activity were present in all villus enterocytes. In hypolactasic tissues, lactase mRNA was detected only in some villus enterocytes; some of them also expressed protein and activity, whereas others did not. In 8 of these hypolactasic samples, a variable number of villus enterocytes with lactase mRNA and protein did not express lactase activity. Various types of enterocytes are present even on a single villus from individuals with adult-type hypolactasia. These results show that different mechanisms control lactase expression in enterocytes on the same villus.