W. Ann Reynolds

Placental transfer of glutamate and its metabolites in the primate

When radioactive glutamate was infused into pregnant rhesus monkeys, 69 to 88 per cent of radioactivity in the maternal plasma remained in association with glutamate while 10 to 22 per cent was converted to glucose. In the fetal plasma, glucose and lactate accounted for more than 80 per cent of radioactivity, with less than 2 per cent of the label found in glutamate. Maternal glutamate infusions resulting in a ten- to twenty-fold increase in maternal plasma glutamate levels (60 to 100 mumoles per 100 ml.) had no effect upon fetal glutamate levels. Infusions producing maternal glutamate levels 70 times normal (280 mumoles per 100 ml.) did result in some transfer of glutamate to the fetal circulation. Labeled glutamate administered to the fetus at 1.5 to 2.4 Gm. per kilogram of fetal weight did not result in glutamate transfer to the maternal circulation. Infusion of glutamate to the fetus at 5 Gm. per kilogram of fetal weight increased fetal plasma glutamate levels to 2, 000 mumoles per 100 ml. and resulted in some transfer of glutamate to maternal circulation. Glutamate metabolites (lactate and glucose) were readily transferred across the placenta in either direction. These studies indicate that the primate placenta is virtually impermeable to glutamate unless extreme elevations of plasma glutamate are induced.

Calcitropic hormone responsiveness during pregnancy

Release of the calcitropic hormones parathyroid hormone (PTH) and calcitonin (CT) in-response to provocative stimuli was assessed in pregnant rhesus monkeys tested three times during gestation (corresponding to the end of each trimester) and again 6 weeks post partum. In the case of PTH, although basal levels were higher during pregnancy than post partum and tended to increase with advancing gestation, similar to observations in human subjects, the incremental response of the hormone to a hypocalcemic stimulus was diminished in pregnant animals and tended to lessen with advancing gestation. Basal CT levels were also increased during pregnancy but, in contrast to PTH, the incremental CT response to a provocative stimulus was generally greater during pregnancy than post partum and tended to increase with advancing gestation. The explanation of these findings may lie in differing degrees of hormone storage. These adjustments in maternal endocrine physiology regulating calcium metabolism would have the net effect of tending to preserve the maternal skeleton by protecting it from excessive resorption at times of hypocalcemia and promoting increased calcium storage during episodes of hypercalcemia.

Hemoglobin AIc in the Glucose-intolerant, Streptozotocin-treated or Pancreatectomized Macaque Monkey

Hemoglobin AIc (Hb AIc), a glycosylated minor variant of Hb A, is elevated in diabetic patients. In our study, macaque monkey model with acquired glucose intolerance [both streptozotocin (STZ)-treated or pancreatectomized] was evaluated for the presence of Hb AIc and for evidence of a possible physiologic effect on oxygen-carrying capacity. Blood from 29 Macaca monkeys (27 rhesus), including 22 with carbohydrate intolerance (17 treated with STZ and five that were pancreatectomized), was analyzed for minor hemoglobins using Amberlite IRC-50 with cyanide-phosphate elution. Unlike in man, no Hb AIc peak was identified in any control animals. However, all five pancreatectomized animals and 10 of 17 STZ-treated animals had clearly identified peaks that eluted similarly to human AIc and had an increased glucose content after acid hydrolysis relative to the major Hb A peak. Of the more severely carbohydrate-intolerant animals (fasting blood sugar > 200 mg. per deciliter) that were receiving insulin, seven of eight monkeys had Hb AIc. peaks compared with seven of 14 animals with less severe carbohydrate intolerance (fasting blood glucose < 200 mg. per deciliter) treated without insulin. During pregnancy, none of the seven STZ-treated animals had a definite peak, although one of these animals demonstrated an Hb AIc peak postpartum. In a group of five control and three STZ-treated nonpregnant animals, no differences were observed in whole blood pH, PCO2, P50, 2,3-diphosphoglycerate, adenosine triphosphate, and adenosine diphosphate, and plasma inorganic phosphate, while plasma glucose was variably elevated. The glucose-intolerant macaque model has potential for studying the long-term effects of acquired hyperglycemia, the biochemistry of the glycohemoglobin, and the possible pathophysioiogic effects of Hb AIc in pregnancy.

Maternal and Fetal Plasma Levels of 3-Methylhistidine in Pregnant Nonhuman Primates

Available data indicate little reutilization of 3-methylhistidine (3-MH) in the rat and man. These data led to the use of urinary 3-MH excretion as a measure of muscle protein catabolism in those animal species. However, 3-MH excretion does not accurately measure protein catabolism in the sheep, pig, and rabbit. This is due, at least in part, to the fact that renal amino acid (AA) transport systems reabsorb 3-MH from the glomerular filtrate. The monkey differs from man in that its plasms contains significant quantities of 3-MH, suggesting an active renal transport system for this AA. The present study measured maternal and fetal plasma 3-MH levels in 33 pregnant rhesus monkeys to determine whether the non-human primate placenta contained transport sites concentrating this AA to the fetal plasma. Mean fetal plasma 3-MH concentrations were 16.4 +/- 6.71 micrometers/100 ml, while maternal levels were 9.45 +/- 3.69 micrometers/100 ml. The fetal to maternal gradient was maintained between 1.6 to 1.7 during the course of maternal infusions of various AA. Since placental AA transport systems are similar to those in the kidney and intestine, the data also suggest the presence of AA transport systems for 3-MH in the monkey, indicating that urinary 3-MH excretion would be a poor method for measuring muscle protein catabolism in this species.