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IP Georgiev, TM Georgieva, M Pfaffl, HM Hammon, and JW Blum

Intestinal development is modified by age and nutrition, mediated in part by insulin-like growth factors (IGF-I, IGF-II) and insulin. We have investigated whether expression of IGF-I, IGF-II and insulin receptors (IGF-IR, IGF-IIR and IR; measured by real-time RT-PCR) and binding capacity (Bmax) of IGF-IR, IGF-IIR and IR in the mucosa of the small and large intestine of neonatal calves are modified by age and different feeding regimes. In experiment 1, pre-term (GrP) and full-term (GrN) calves (after 277 and 290 days of pregnancy respectively) were killed immediately after birth before being fed; a further group of full-term calves were fed for 7 days and killed on day 8 of life (GrC(1-3)). In experiment 2, full-term calves were killed on day 8 after being fed first-colostrum for 7 days (GrCmax), colostrum of the first six milkings for 3 days (GrC(1-3)) or milk-based formula for 3 days (GrF(1-3)). Intestinal sites differed with respect to expression levels of IGF-IR (duodenum>jejunum in GrC(1-3); ileum>colon, duodenum> or = jejunum in GrF(1-3)), IGF-IIR (colon>duodenum and ileum in GrN), and IR (lowest in ileum in GrP and CrN; highest in colon in GrC(1-3) and GrCmax). They also differed with respect to Bmax of IGF-IR (ileum and colon>duodenum and jejunum in GrP; ileum and colon>jejunum in GrN; colon>jejunum in GrC(1-3); lowest in jejunum in GrF(1-3)), IGF-IIR (duodenum and colon>jejunum and ileum in GrP; duodenum>ilem and colon>jejunum in GrN; duodenum, jejunum and colon>ileum in GrCmax, GrC(1-3), and GrF(1-3)) and IR (ileum>duodenum, jejunum and colon in GrCmax, GrC(1-3), and GrF(1-3)). There were significant differences between groups in the expression of IGF-IR (GrF(1-3)> GrCmax and GrC(1-3) in ileum), IGF-IIR (GrN>GrP and GrC(1-3) in colon; GrN>GrC(1-3) in jejunum and total intestine), and IR (GrCmax>GrF(1-3) in colon) and in the Bmax of IGF-IR (GrP>GrN in colon; GrCmax>GrF(1-3) in jejunum), IGF-IIR (GrN>GrP in duodenum, ileum and total intestine; GrN>GrC(1-3) in duodenum, ileum, colon and total intestine) and IR (GrN>GrP in total intestine; GrC(1-3)>GrN in ileum and total intestine). In addition, Bmax values of IGF-IR, IGF-IIR and IR were correlated with villus circumference, villus height/crypt depth and proliferation rate of crypt cells at various intestinal sites. There were marked differences in Bmax of IGF-IR, IGF-IIR and IR dependent on mRNA levels, indicating that differences in Bmax were the consequence of differences in posttranslational control and of receptor turnover rates. In conclusion IGF-IR, IGF-IIR and IR expressions and Bmax in intestinal mucosa were different at different intestinal sites and were variably affected by age, but not significantly affected by differences in nutrition. Receptor densities were selectively associated with intestinal mucosa growth.