Expression of the insulin-like growth factor-II/mannose-6-phosphate receptor in multiple human tissues during fetal life and early infancy

The insulin like growth factor-II/mannose-6-phosphate (IGF-II/M6P)
receptor has been detected in many cells and tissues. In the rat,
there is a dramatic developmental regulation of IGF-II/M6P receptor
expression, the receptor being high in fetal and neonatal tissues
and declining thereafter. We have systematically studied the
expression of the human IGF-II/M6P receptor protein in tissues from
10 human fetuses and infants (age 23 weeks gestation to 24 months
postnatal). We have asked 1) whether there is differential
expression among different organs, and 2) whether or not the human
IGF-II/M6P receptor is developmentally regulated from 23 weeks
gestation to 24 months postnatal. Protein was extracted from human
tissues using a buffer containing 2% sodium dodecyl sulfate and 2%
Triton X-100. Aliquots of the protein extracts were analyzed by
sodium dodecyl sulfate- polyacrylamide gel electrophoresis and
immunoblotting using an anti-IGF- II/M6P receptor antiserum (no.
66416) and 125I-protein A or an immunoperoxidase stain. IGF-II/M6P
receptor immunoreactivity was detected in all tissues studied with
the highest amount of receptor being expressed in heart, thymus,
and kidney and the lowest receptor content being measured in brain
and muscle. The receptor content in ovary, testis, lung, and spleen
was intermediate. The apparent molecular weight of the IGF-II/M6P
receptor (220,000 kilos without reduction of disulfide bonds)
varied among the different tissues: in brain the receptor was of
lower molecular weight than in other organs. Immunoquantitation
experiments employing 125I-protein A and protein extracts from
human kidney at different ages revealed a small, albeit not
significant, difference of the receptor content between fetal and
postnatal tissues: as in other species, larger amounts of receptor
seemed to be present in fetal than in postnatal organs. In
addition, no significant difference of the receptor content between
human fetal liver and early postnatal liver was measured employing
125I-protein A- immunoquantitation in three fetal and five
postnatal liver tissue samples. The distribution of IGF-binding
protein (IGEBP) species, another abundant and major class of IGF
binding principles, was also measured in human fetal and early
postnatal lung, liver, kidney, muscle, and brain using Western
ligand blotting with 125I-IGF-II: as with IGF-II/M6P receptor
immunoreactivity there was differential expression of the different
classes of IGFBPs in the various organs.