TRANSCRIPTIONAL REGULATION OF INTESTINAL HYDROLASE BIOSYNTHESIS DURING POSTNATAL-DEVELOPMENT IN RATS

Lactase-phlorizin hydrolase (LPH) and sucrase-isomaltase (SI) are inte stine-specific microvillus membrane hydrolases whose specific activiti es demonstrate reciprocal regulation during development but whose mech anisms of regulation have not been fully defined. To investigate trans criptional control of these two proteins, the rat LPH and SI genes wer e cloned, and antisense probes for preprocessed mRNAs (pre-mRNAs) were developed from intron sequence. LPH mRNA, as measured by quantitative ribonuclease (RNase) protection assays, was abundant before weaning a nd decreased two- to fourfold during weaning, whereas SI mRNA was firs t detected 14 days after birth and increased rapidly to abundant level s by age 28 days. LPH and SI pre-mRNA levels paralleled those of their respective mRNAs. LPH transcriptional rate declined during weaning, w hereas that of SI increased during this time as determined by RNase pr otection assays of pre-mRNAs and nuclear run-on assays. In the adult r at, LPH mRNA was restricted to the jejunum and proximal ileum, whereas SI mRNA was detected throughout the small intestine, a pattern regula ted by transcriptional rate as confirmed by nuclear run-on assays. Lac tase and sucrase specific activities correlated well with their respec tive protein and mRNA concentrations in all experiments. We conclude t hat gene transcription plays a major role in the developmental and hor izontal regulation of LPH and SI biosynthesis and that these two genes are regulated differently in rat small intestine.