Enhanced growth of small bowel in transgenic mice expressing human insulin-like growth factor I.
OBJECTIVE
Growth hormone and insulin-like growth factor I (IGF-I) stimulate small bowel growth. The aim of this study was to analyze whether IGF-I mediates enterotrophic actions of growth hormone.


METHODS
IGF-I transgenic mice that overexpress an IGF-I transgene driven by the mouse metallothionein I promoter and are growth hormone deficient were compared with wild-type littermates. Growth of small bowel, abundance and localization of messenger RNAs for the IGF-I transgene, and insulin-like growth factor-binding protein 3 were assayed.


RESULTS
Small bowel length and mass were greater in IGF-I transgenic mice than in wild-type mice. Villus height, crypt depth, and crypt cell mitoses were greater in jejunum of transgenics than wild-type mice, but jejunal disacharidase activities were not increased. The transgene was expressed strongly in villus epithelial cells. Insulin-like growth factor-binding protein 3 messenger RNA was localized in the lamina propria. Regional expression of both correlated with the increase in mucosal mass.


CONCLUSIONS
Effects of IGF-I overexpression on intestinal length and mucosal mass were similar to effects of growth hormone overexpression observed previously. Excess of IGF-I increased crypt cell proliferation, whereas excess of growth hormone did not increase crypt cell proliferation. IGF-I excess stimulated differentiation of intestinal epithelial cells less effectively than growth hormone excess.
Ohneda
K
K
Department of Physiology, University of North Carolina at Chapel Hill, USA.
Ulshen
M H
MH
Fuller
C R
CR
D'Ercole
A J
AJ
Lund
P K
PK
D000818:Animals; D001835:Body Weight; D002417:Cattle; D002149:Energy Intake; D015870:Gene Expression; D013006:Growth Hormone / Q000235:genetics; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000254:growth & development / Q000502:physiology; D007421:Intestine, Small / Q000033:anatomy & histology / Q000166:cytology / Q000254:growth & development*; D007583:Jejunum / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D008938:Mitosis; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D014018:Tissue Distribution
D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone