IGF-I as a mediator of VIP/activity-dependent neurotrophic factor-stimulated embryonic growth.
IGF-I and the IGF-I receptor are necessary for normal embryonic growth. VIP is an important regulator of early postimplantation growth and acts indirectly through the release of other factors, including activity-dependent neurotrophic factor. The relationship of IGF-I growth regulation to VIP/activity-dependent neurotrophic factor-stimulated growth was examined with whole cultured embryonic d 9.5 mouse embryos. Somite numbers and DNA and protein contents were measured in embryos treated with IGF-I, anti-IGF-I, VIP, activity-dependent neurotrophic factor, and anti-activity-dependent neurotrophic factor-14 (antiserum to an activity-dependent neurotrophic factor agonist). IGF-I mRNA content was measured after incubation with and without VIP for 30 and 60 min using competitive RT-PCR. IGF-I induced a significant, dose-dependent increase in growth as measured by somite number, DNA levels, and protein content. Furthermore, anti-IGF-I inhibited embryonic growth and also prevented exogenous IGF-mediated growth. Both VIP- and activity-dependent neurotrophic factor-stimulated growth were blocked by anti-IGF-I, whereas anti-activity-dependent neurotrophic factor-14 had no detectable effect on IGF-I-induced growth. Treatment with VIP resulted in a 2-fold increase in embryonic IGF-I mRNA. These data suggest that IGF-I is a downstream mediator of VIP and activity-dependent neurotrophic factor in a regulatory pathway coordinating embryonic growth and that VIP may function as a regulator of IGF-I gene expression in the embryo.
Servoss
S J
SJ
Section on Developmental and Molecular Pharmacology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Lee
S J
SJ
Gibney
G
G
Gozes
I
I
Brenneman
D E
DE
Hill
J M
JM
D000818:Animals; D046508:Culture Techniques; D004622:Embryo, Mammalian / Q000502:physiology*; D005314:Embryonic and Fetal Development / Q000187:drug effects / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology / Q000502:physiology*; D009479:Neuropeptides; D009842:Oligopeptides; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology / Q000502:physiology*
D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009842:Oligopeptides; D012333:RNA, Messenger; C410622:activity-dependent neurotrophic factor; D014660:Vasoactive Intestinal Peptide; D007334:Insulin-Like Growth Factor I