14 research outputs found
The IGF system during growth and differentiation of the mouse
The insulin-like growth factors (IGFs) were first discovered in 1957 by Salmon and
Daughaday (1957). They found that in vivo administration of growth hormone (GH)
induced a serum factor capable of stimulating sulfate uptake in cartilage. In 1972 this
'sulfation factor' was renamed somatomedin (mediator of the effects of somatotropin,
GH) and classified as a growth factor (Daughaday et aI., 1972). At the same time, a
compound named NSILA (nonsuppressible insulin-like activity) was found (Froesch et aI.,
1966). NSILA and somatomedin each stimulated glucose incorporation into fat and sulfate
incorporation into cartilage (Froesch et aI., 1976). The amino acid sequence of NSILA
showed 48% homology with human pro-insulin. Therefore it was called insulin-like
growth factor-I (IGF-I) (Rinderknecht and Humbel, 1978a). A second bioactive insulin-like
molecule appeared to be similar, but not identical, and was named IGF-II (Rinderknecht
and Humbel, 1978b). Somatomedin appeared to be identical to IGF-I (Svoboda et aI.,
1980).
Now, over forty years later, in vivo studies, gene expression experiments, and
determination of signalling pathways have provided more insight into IGF actions. IGF
receptors and IGF binding proteins (IGFBPs) have been characterized (Chernausek et aI.,
1981; Kasuga et aI., 1981; Brinkman et aI., 1988; Binkert et aI., 1989; Margot et aI.,
1989; Shimasaki, 1989; Murphy et aI., 1990; Shimasaki, 1990; 1991a/b; Schuller et aI.,
1994). This, and the recent discovery of IGFBP related proteins, have shown the
complexity of the IGF system (Oh et aI., 1996). It is clear that the IGFs, together with the
other IGF system compounds, playa pivotal role in body and organ development and
growth.
Therefore, this chapter will review in more detait characteristics of the separate
components of the IGF system. Then, focus is put on the IGF system during mouse
development. A summary of the data generated to elucidate the functions of the IGF
system during mouse development is described
The role of the IGF axis in IGFBP-1 and IGF-I induced renal enlargement in Snell dwarf mice
Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is generally
believed to inhibit IGF action in the circulation. In contrast, IGFBP-1
has been reported to interact with cell surfaces and enhance IGF-I action
locally in some tissues. Renal IGFBP-1 levels are found elevated in
various conditions characterized by renal growth (e.g. diabetes mellitus,
hypokalemia). To test whether IGFBP-1 is a renotropic factor, IGFBP-1 was
administered alone or in combination with IGF-I to Snell dwarf mice, an in
vivo model without compensatory feedback effects on growth hormone (GH)
secretion. In three control groups of Snell dwarf mice, placebo, GH or
IGF-I was administered. Compared with placebo, kidney weight increased in
all treated groups, however, with different effects on kidney morphology.
Administration of IGF-I, alone or in combination with IGFBP-1, tended to
increase glomerular volume, while no changes were seen in the other
groups. Administration of IGFBP-1 or IGFBP-1+IGF-I both caused dilatation
of the thin limbs of Henle's loop, while GH or IGF-I administration had no
visible effect. Furthermore, IGF-I administration resulted in an increased
mean number of nuclei per cortical area and renal weight, whereas GH,
IGF-I+IGFBP-1 or IGFBP-1 caused a decreased renal nuclei number. In situ
hybridization and immunohistochemistry showed specific changes of the
renal IGF system expression patterns in the different groups.
Particularly, IGFBP-1 administration resulted in extensive changes in the
mRNA expression of the renal IGF system, whereas the other administration
regimen resulted in less prominent modifications. In contrast,
administration of IGFBP-1 and IGFBP-1+IGF-I resulted in identical changes
in the protein expression of the renal IGF system. Our results indicate
that IGFBP-1, alone or in combination with IGF-I, demonstrated effects on
the renal tubular system that differ from the effects of IGF-I