METABOLISM OF C-PEPTIDE IN THE PREGNANT RHESUS MONKEY

Abstract

The assessment of fetal and maternal B-cell function by C-peptide measurement requires an understanding of its metabolism in pregnancy. We gave 125I-tyrosylated-C-peptide (I-CP) to 6 pregnant Rhesus monkeys by bolus followed by constant infusion. This resulted in a steady state in the maternal circulation of immunoprecipitable cpm, as measured using excess C-peptide antiserum. At the end of the 2 or 4 hr infusion fetuses were exsanguinated via the umbilical vein. In the umbilical venous plasma (UVP) 3-13% of total cpm were immunoprecipitable. UVP immunoprecipitable cpm represented 1.4-5.8% of maternal immunoprecipitable cpm at delivery. Medium pressure gel filtration chromatography of UVP showed that the immunoprecipitable cpm were due to & fragment of I-CP approximately 25 amino acids long. The predominant immunoprecipitable peak in maternal plasma was intact I-CP; a peak corresponding to the fetal immunoprecipitable peak was also present. Simultaneous maternal arterial and uterine vein samples showed that the degradation of I-CP occured across the uterus. Comparison to studies in 3 post-partum animals indicated that pregnancy increased the rate of appearance of I-CP metabolites. Further, when I-CP was incubated with trophoblastic cells in culture, degradation to the fetal immunoreactive species was observed. We conclude that pregnancy alters maternal C-peptide metabolism, owing largely to placental metabolism. Though placental passage was insufficient to alter interpretation of fetal measurements, the placenta may degrade fetal C-peptide.