CERULOPLASMIN AND COPPER TRANSPORT DURING THE LATTER PART GESTATION IN THE RAT

We have examined the tissue uptake of Cu-67 from ceruloplasmin versus albumin and transcuprein, after its intravenous administration to preg nant rats, in the last 4 days of gestation. Cu-67 infused as in vivo-l abeled ceruloplasmin remained on ceruloplasmin in the maternal circula tion over the 4- to 6-hr time period examined, as determined by gel ch romatography and immunoreactivity. That infused as in vitro-labeled se rum was initially on transcuprein and albumin but soon also with new c eruloplasmin. On the basis of percent dose as well as total actual Cu transferred (taking into account the sizes of the two plasma Cu pools) , ceruloplasmin was the preferred source of Cu for most tissues. Total uptake of Cu from ceruloplasmin was seven times greater than that fro m albumin and transcuprein for the placenta, whole fetus, and fetal li ver. It was 2- to 6-fold greater for other tissues (except liver and k idney). When synthesis of maternal Cu-67-ceruloplasmin (from Cu-67 adm inistered on albumin and transcuprein) was inhibited with cycloheximid e, uptake by nonhepatic tissues was reduced markedly. In the fetal cir culation, entering 67(Cu) was initially associated with transcuprein a nd alpha-fetoprotein (or albumin), but then also appeared with cerulop lasmin. Specific receptors for ceruloplasmin were detected on membrane s from the placenta as well as fetal liver; mRNA for ceruloplasmin was detected on the endoplasmic reticulum-bound polyribosomes of placenta /yolk sac, and of fetal and maternal liver. We conclude that Cu destin ed for the fetus is delivered mainly or exclusively by ceruloplasmin. It may enter via placental receptors, arriving in fetal plasma in ioni c form, for later incorporation into fetal ceruloplasmin. The importan ce of ceruloplasmin as a source of plasma Cu for nonhepatic organs is also confirmed.