Mammalian hexokinase types one and three (HK1 and HK3) are 100 kDa iso
zymes that phosphorylate glucose to glucose-6-phosphate. HK1 is presen
t in most tissues but is especially prominent in brain and kidney. HK3
is less well studied, but may be most prominent in the spleen and lym
phocytes. In this study, we determined the ontogeny of the expression
of these isoforms in the rat. Using immunohistochemistry, we identifie
d HK1 and HK3 immunoreactivity in the brain, heart, kidney, liver, ske
letal muscle and spleen from gestational day 14 (E14) to 45 days after
birth (P45). With the exception of the liver and spleen, we observed
a similar age-and cell-dependent staining pattern for both isoforms in
all organs studied. The brain and spleen were analyzed in more detail
to identify specific regions of immunoreactivity during maturation. A
transient expression of HK1 and HK3 was noted in the cell bodies of m
ature neurons, including layers V and VI of the cerebral cortex and th
e cerebellar Purkinje cells followed by localization to the white matt
er of the cerebrum and cerebellum. In the spleen, HK3 immunoreactivity
was detected postnatally and appeared to track with the infiltration
of B cells. Our demonstration of changing patterns of immunoreactivity
for HK1 and HK3 in fetal and postnatal organs suggests that these HK
isoforms are involved the process of development. We speculate that HK
1 and HK3 share a complex interaction during development of these orga
ns and regulate glucose metabolism at multiple levels during developme
nt.