AGE-DEPENDENT INCREASE OF NEUROTENSIN EXPRESSION IN THE ILEUM

The proliferative activity of gut mucosa is increased with aging. Neur otensin (NT), a tridecapeptide localized to the distal small bowel, st imulates growth of gut mucosa; the effects of aging on gut NT are not known. Young (4-mo-old), adult (l-yr-old), and aged (2-yr-old) male Fi scher 344 rats were killed; the ileal mucosa was scraped, weighed, and extracted for measurement of NT mRNA by slot-blot and Northern hybrid ization; and the relative NT transcription rate was determined by a nu clear run-on assay. In addition, NT tissue content and plasma levels w ere determined by radioimmunoassay, and full-thickness sections of ile um were examined for age-dependent alterations of NT endocrine cell (N -cell) number using immunohistochemical staining. Slot-blot and Northe rn-blot analyses showed that the steady-state levels of NT mRNA were i ncreased threefold in the adult group and eightfold in the aged rats. In addition, NT peptide content and plasma levels were significantly i ncreased in the aged group. The dramatic increases in the abundance of NT mRNA were not associated with increases in either NT transcription or N-cell number. In summary, we have demonstrated an age-dependent i ncrease in the constitutive levels of ileal NT mRNA that appears not t o be due to concomitant increases in transcription, suggesting that NT mRNA is increased by mechanisms involving mainly a posttranscriptiona l process. In addition, we have shown corresponding increases in the l evels of both tissue and plasma NT with aging, indicating that express ion of NT does not remain the same throughout life but actually increa ses with aging in the rat.