Project Details
Description
Alpha fetoprotein (AFP) is a glycoprotein which is produced in high
amounts during pregnancy. Biochemically, AFP exhibits charge lectin
microheterogeneity. Results from our laboratory have shown that the
microheterogeneous nature of AFP changes markedly during normal
development. However, it is currently not certain if these findings
reflect a physiological change in AFP function or merely indicate an
alteration in the biochemistry of this glycoprotein.
AFP isolated from term core blood, although not mitogenic itself, can
enhance the mitogenic activity of growth factors and may function to
modulate cell proliferation during fetal development. No mitogenic
activity was observed in midgestation amniotic fluid, which also
contains increased levels of AFP. Thus, AFP proliferative activity may
vary with fetal development. The relationship between developmental
changes in AFP microheterogeneity and biological activity is of major
interest.
In the series of experiments proposed herein, we will attempt to
characterize the developmental aspects of AFP microheterogeneity and
biological activity. We will use the monkey as a model to carefully
define these ontogenic changes and to compliment and extend data
obtained from the use of human fetal material, which is obviously
limited. The charge and lectin microheterogeneity of AFP will be
evaluated in the species throughout gestation. Monkey fetal tissue will
be removed at various stages of gestation to allow the characterization
of the production of AFP by these tissues. Additionally, we will use
both the monkey and the human to elucidate the relationships between
charge and lectin microheterogeneity and the expression of AFP
proliferative activity. Finally, the biochemical basis for AFP
microheterogeneity and biological activity will be elucidated. The
results of these studies will greatly add to our knowledge of the
biochemical and physiological importance of AFP to normal fetal
development.
Status | Not started |
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