Comparison of leucine, serine and glycine transport across the ovine placenta

To estimate the transport rate of maternal glycine across the placenta [1-13C]glycine and L-[1-13]serine were infused intravenously in pregnant sheep using both continuous and bolus infusions. Each tracer was infused together with L-[1-13C]leucine, to enable a comparison with the placental transport of an essential amino acid. At steady state, fetal plasma leucine enrichment was 40 per cent of maternal enrichment, indicating that approximately 60 per cent of the entry rate of leucine into fetal plasma is derived from protein breakdown in the placenta and fetus. Fetal plasma glycine enrichment was 11 per cent of maternal and there was no detectable fetal serine enrichment. The direct flux of maternal leucine into the fetal circulation was approximately 3.0 (bolus experiments) to 3.6 (continuous infusion experiments) mumol/min (kg fetus) and greater than the estimated 1.4 mumol/min (kg fetus) direct flux of maternal glycine, despite the fact that the net umbilical uptake of glycine exceeds that of leucine. This supports the conclusion that placental glycine production is a quantitatively important contribution to fetal glycine uptake via the umbilical circulation. The fetal glycine supply from the placenta is provided by a relatively small direct maternal glycine transplacental flux and a larger contribution derived from serine utilization within the placenta for glycine production.     

Transplacental transfer and biotransformation studies of nicotine in the human placental cotyledon perfused in vitro

Our objective was to study the characteristics of transfer and biotransformation of nicotine in the human term placenta. Nicotine transfer was studied by dually perfusing an isolated cotyledon of the human placenta in vitro. Nicotine metabolism to cotinine was investigated in intact tissue during perfusion and in placental microsomal fractions. Following the addition of nicotine (40 ng/ml) to the maternal side of the placenta, distribution into placental tissue (0.43 +/- 0.13 ng/ml/min) was three times higher than transfer to the fetal side of the placenta (0.15 +/- 0.01 ng/ml/min). The steady-state maternal-to-fetal transfer of nicotine was approximately 90% that of antipyrine (a marker of flow-dependent transfer). There was no evidence of nicotine metabolism to cotinine by intact placental tissue or in microsomal fractions. The observation that nicotine readily crosses the human placenta with no evidence of metabolism suggests that nicotine has the potential to cause adverse affects on the developing fetus.     

Incorporation in vivo of 1-14C-palmitic acid into placental and fetal liver lipids of the rabbit

The incorporation of free fatty acid into the placental and fetal liver lipids of rabbits was studied after fetal injections of albumin-bound 1-14C-palmitic acid. The fetuses were killed either 5--10 or 10--20 min after the injection. The placentas and livers were extracted for lipids and the specific activities of triglycerides (TG), phospholipids (PL), free fatty acids (FFA), monoglycerides (MG) and diglycerides (DG) measured. The lipids of the liver and placenta took up 17.0 and 3.6% of the dose, respectively, and of that liver TG accounted for 74% and the placental TG 34% of the label in each tissue. Most of the remaining counts were in the PL fraction with the rest more or less evely distributed between the FFA, DG and MG fractions. No activity was recorded in the cholesterol esters. The placental TG, PL, DG and MG specific activities reached the same level as that of the placental FFA, while in the liver these esters had higher specific activities (than the liver FFA). The liver TG, DG and PL had higher specific activities when compared with those of the placenta. The specific activity of the placental FFA was lower at 10--20 min than at 5--10 min; the opposite was seen for the placental TG. No time-related changes were seen in the liver lipids. It is concluded that (i) both placenta and fetal liver incorporate FFA into glycerides and PL; (ii) the liver incorporates FFA more rapidly and to a greater extent than the placenta; (iii) most of the FFA is incorporated into TG and to a lesser extent (PL; (iv) in both organs hydrolysis of PL or TG occurs. These results are discussed with reference to placental transport of FFA and fetal fat metabolism.     

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On day 21.5 a pregnant rat received a single injection of [1-14C]glycerol. The purpose was to study the transfer of glycerol through the placenta from the maternal to fetal plasma. From 3-20 min after injection the specific activity of glycerol in maternal and fetal plasma was measured. The results indicate that the mother can provide this molecule to the fetus. Similar results were obtained with the rabbit on day 28 of pregnancy. The possibility of the conversion of plasma glycerol to glucose has been investigated in the rat and rabbit fetus. This molecule was chosen chiefly to see whether the gluconeogenic pathway was functioning in the fetus above the triose phosphate step. At two stages of fetal development the capacity of the fetus to incorporate [1-14C]glycerol into glucose plus glycogen has been shown in the two species. In the rat fetus the conversion of [1-14C]glycerol to [14C]glucose increases from 19.5 to 21.5 days of gestation. For the rabbit this parameter increases from 25 to 28 days of gestation. On day 25 in the rabbit and day 19.5 in the rat the liver glycogen was labeled, but it did not accumulate the [14C]glucose from [1-14C]glycerol during the time that we have studied. In contrast, on day 28 in the rabbit and day 21.5 in the rat the incorporation of radioactivity increased as function of the time. However, the relative importance of glycerol as precursor of the glucose plus glycogen in the fetus remains to be elucidated.     

Postmaturity in the rat: glucose metabolism in the fetus and the neonate

The present study was designed to investigate glucose metabolism in the postmature fetus and newborn. In the fetus, the decreased hepatic glycogen content together with the decrease by the same percentage of total hepatic glycogen radioactivity from directly injected [6-3H]glucose demonstrate that fetal glycogenolysis occurs during prolonged gestation. Moreover, fetal glycogen synthesis as tested by in vivo [6-3H]glucose incorporation experiments is inhibited. In vivo experiments with [14C]lactate are consistent with gluconeogenesis, being inactive in the postmature fetus as well as in the normal-term fetus. During the first hr after delivery, our in vivo data about conversion of [14C]lactate to glucose show that the gluconeogenic pathway is not functioning in spite of very high phosphoenolpyruvate carboxykinase activity in the postmature. By 3 hr postpartum, the phosphoenolpyruvate carboxykinase activity, the blood lactate level, the percentage of conversion, and the rate of gluconeogenesis are very elevated in the postmatures as compared to the term neonates. By 6 hr postpartum, despite maintained phosphoenolpyruvate carboxykinase activity, gluconeogenic rate becomes very weak in postmatures kept fasting. This is the time characterized by a profound hypoglycemia. In contrast, fed postmature neonates exhibit normal blood glucose levels by 6 and 12 hr postpartum as a result of sustained rate of gluconeogenesis.     

Influence of a fat-free diet on the content and synthesis of arachidonic acid in the feto-placental unit of the rat

In rats receiving a fat-free food throughout the period of pregnancy, the individual fatty acids of total lipids from placenta, total fetus, maternal and fetal serum were determined quantitatively on day 21/22 of pregnancy. Also, the incorporation of 14C-acetate in vitro into placental fatty acids, divided by the number of double bonds, was measured and the rate of synthesis calculated therefrom. The fat-free diet caused a drastic fall of linoleic acid concentration in maternal serum and all fetal compartments. On the contrary, the amount of arachidonic acid remained almost unchanged in fetal serum and total fetus, and even slightly increased in placenta. In the maternal serum, too, the arachidonic acid concentration remained constant under fat-free diet. The observed concentration changes of single fatty acids in the maternal serum are reflected in all fetal compartments and led to a rise in total fatty acids in all sera and tissues studied. The height of rise decreased in the order: maternal serum less than placenta less than fetal serum less than total fetus. The rate of synthesis for arachidonic acid in placenta was on day 21/22 of pregnancy 0.3 (controls) and 0.5 (fat-free diet) micrometer/100 g placenta and hour, being able to cover the placenta's own need to less than one-third. The results suggest that the protection of the feto-placental unit against arachidonic acid deficiency under fat-free diet of the mother is provided mainly by a constant supply of maternal unit with arachidonic acid under normal conditions has to be ensured essentially by the mother.     

Gluconeogenesis and intrahepatic triose phosphate flux in response to fasting or substrate loads. Application of the mass isotopomer distribution analysis technique with testing of assumptions and potential problems

We measured gluconeogenesis (GNG) in rats by mass isotopomer distribution analysis, which allows enrichment of the true biosynthetic precursor pool (hepatic cytosolic triose phosphates) to be determined. Fractional GNG from infused [3-13C]lactate, [1-13C]lactate, and [2-13C]glycerol was 88 +/- 2, 89 +/- 3, and 87 +/- 2%, respectively, after 48 h of fasting. [2-13C]Glycerol was the most efficient label and allowed measurement of rate of appearance of intrahepatic triose phosphate (Ra triose-P), by dilution. IV fructose (10-15 mg/kg/min) increased absolute GNG by 81-147%. Ra triose-P increased proportionately, but endogenous Ra triose-P was almost completely suppressed, suggesting feedback control. Interestingly, 15-17% of fructose was directly converted to glucose without entering hepatic triose-P. IV glucose reduced GNG and Ra triose-P. 24-h fasting reduced hepatic glucose production by half, but absolute GNG was unchanged due to increased fractional GNG (51-87%). Reduced hepatic glucose production was entirely due to decreased glycogen input, from 7.3 +/- 1.8 to 1.1 +/- 0.2 mg/kg/min. Ra triose-P fell during fasting, but efficiency of triose-P disposal into GNG increased, maintaining GNG constant. Secreted glucuronyl conjugates and plasma glucose results correlated closely. In summary, GNG and intrahepatic triose-P flux can be measured by mass isotopomer distribution analysis with [2-13C]glycerol.     

XH-14 analogues as adenosine antagonists

To investigate the utilization of dietary amino acids for hepatic protein synthesis, seven female pigs ( 28 d old, 7.5 kg) were implanted with catheters in a carotid artery, the jugular and portal veins, and the stomach. A portal flow probe was also implanted. The pigs were fed a high protein diet once hourly and infused intragastrically with [U-13C]algal protein for 6 h. Amino acid labeling was measured in arterial and portal blood, in the hepatic free and protein-bound pools and in apolipoprotein B-100 (apoB-100), albumin and fibrinogen. The isotopic enrichments of apoB-100-bound [U-13C]threonine, leucine, lysine and phenylalanine were 33, 100, 194 and 230% higher than those of their respective hepatic free amino acid pools (P < 0.01). Using the labeling of apoB-100 to estimate that of the protein synthetic precursor, the fractional rate of hepatic protein synthesis was 42 +/- 2%/d. Between 5 and 8% of the dietary tracer amino acids was used for hepatic protein synthesis. In contrast to the small intestinal mucosa, in which the majority of the metabolized amino acids were apparently catabolized, protein synthesis utilized from 48% (threonine) to 90% (lysine) of the hepatic uptake of tracer amino acids. It appears that hepatic protein synthesis consumes nutritionally significant quantities of dietary essential amino acids in first pass and that extracellular, especially portal, essential amino acids are channeled to hepatic protein synthesis in the fed state.     

Placental transport of nutrients

The fetus is dependent upon the placenta for transport to it of all nutrients for energy and growth. The primary nutrients crossing the placenta are glucose, lactic acid, free amino acids, free fatty acids, and ketone bodies. Under normal circumstances, it appears that glucose is the primary energy source. In abnormal conditions there is the possibility that energy requirements may be met also by protein-amino acid oxidation and ketone body metabolism. The fetal brain may be quite adept in the use of ketone bodies. In all transport phenomena, the placenta intervenes by diverting nutrients into its own intermediary metabolism. For a more extensive consideration of these factors, several in-depth reviews are recommended. To better understand abnormalities of intrauterine growth, we need much more specific information about the mechanisms of placental transport and the intermediary metabolism of the placenta and fetus. When these are adequately in states of normal and abnormal intrauterine growth, we can then consider methods of metabolic intervention which will correct intrauterine growth failure and, hopefully, eliminate its hazards to the fetus and child.     

Indacrinone: modification of diuretic, uricosuric, and kaliuretic actions by amiloride

1. The metabolism of some vasoactive hormones perfused through pulmonary vessels was studied in samples of human lung obtained at operations. 2. 5-Hydroxytryptamine was inactivated and this inactivation was inhibited by desmehtylimipramine and mebanazine. 3. Beta-[14C]Phenylethylamine was also metabolized in human lung. 4. Prostaglandin E2 was inactivated and this inactivation inhibited by bromocresol green and frusemide. 5. About 10% of the radioactivity from infused [14C]arachidonic acid emerged from the lung and a small amount of biological activation occurred. 6. Of [14C]arachidonic acid retained by the lung, most was present in phopholipid with lesser amounts in neutral lipid and free acid fractions. 7. The fate of the hormones studied was qualitatively similar to their fate in animal lungs.     

Placental diffusing capacities at varied carbon monoxide tensions

To test the hypothesis that carbon monoxide transfer across the placenta is, in part, a facilitated process, we have looked for evidence of saturation kinetics for carbon monoxide. In eight pregnant ewes, fetal to maternal carbon monoxide transfer was examined in a preparation in which the fetal side of the placenta was perfused with blood. The carboxyhemoglobin concentrations on the fetal side of the placenta were varied from 4.8 to 70% in 23 measurements. At increased carbon monoxide tensions, the transfer from fetus to mother always decreased. The slope of log rate of carbon monoxide transfer vs. log partial pressure gradient across the placenta was significantly different from 1. Placental membrane diffusing capacity was calculated separately from total placental diffusing capacity which includes hemoglobin reaction rates and erythrocyte membrane diffusion. Placental membrane diffusing capacity decreased at increased carbon monoxide tensions. Placental permeability for urea did not change with increasing carbon monoxide tensions. These results are consistent with the hypothesis that carbon monoxide diffusion in the placenta is, in part, carrier mediated.     

Exchange of vitamin D3 in placenta and fetal liver

Metabolism of [3H]-vitamin D3 in placenta and fetus liver of rats on the 20-21st day of pregnancy was investigated. Biosynthesis in vivo of 25-hydroxyvitamin D3 occurs in placenta and fetus liver and the maximum observed 25-hydroxylation composes 15% in placenta and 13% in the fetus liver. It has been shown, that C-25-hydroxylation of vitamin D3 in the microsomal and mitochondrial fractions of hepatocytes take place. It has been concluded that placenta and fetus liver, although to not very much degree, is able to realize vitamin D3 metabolism independent of mother's organism.     

Effects of antipyrine on umbilical and regional metabolism in late gestation in the fetal lamb

OBJECTIVE: Antipyrine has been used extensively in fetal metabolic studies and is now known to inhibit prostaglandin synthesis; therefore we wished to determine the effects of antipyrine on fetal umbilical and regional metabolism. STUDY DESIGN: Chronically catheterized fetal lambs were randomly assigned to antipyrine (n = 6) or control (n = 5) groups. Animals in the antipyrine group were infused with antipyrine (mean +/- SD 9.6 +/- 0.9 mg/min for 165 +/- 38 minutes), and control group animals were not infused. Measurements were made of fetal blood gases, oxygen content, glucose, lactate, lower-body blood flow, upper-body flow distribution, and substrate uptakes across the umbilical and hind limb circulations. The unpaired t test, correlation coefficient, and regression analysis were used for comparisons. RESULTS: There were no differences in antipyrine and control group animals with respect to blood gases, metabolite levels, umbilical blood flow, or umbilical uptakes. Hind limb blood flow (p < 0.10) and oxygen uptake (p < 0.05) were lower and lactate production was higher (p < 0.01) in antipyrine animals than in control group animals. Duration of antipyrine exposure correlated directly with hind limb lactate production (r = 0.85, p < 0.001) and inversely with hind limb oxygen uptake (r = -0.65, p < 0.05). The distribution of blood flow within the fetal upper body also differed between groups, with higher cardiac distribution in the antipyrine group (p < 0.025). CONCLUSIONS: Antipyrine does not affect umbilical metabolism but does affect carcass metabolism and fetal blood flow distribution.     

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The time course of incorporation of [14C]arachidonic acid and [3H]docosahexaenoic acid into various lipid fractions in placental choriocarcinoma (BeWo) cells was investigated. BeWo cells were found to rapidly incorporate exogenous [14C]arachidonic acid and [3H] docosahexaenoic acid into the total cellular lipid pool. The extent of docosahexaenoic acid esterification was more rapid than for arachidonic acid, although this difference abated with time to leave only a small percentage of the fatty acids in their unesterified form. Furthermore, uptake was found to be saturable. In the cellular lipids these fatty acids were mainly esterified into the phospholipid (PL) and the triacyglycerol (TAG) fractions. Smaller amounts were also detected in the diacylglycerol and cholesterol ester fractions. Almost 60% of the total amount of [3H]Docosahexaenoic acid taken up by the cells was esterified into TAG whereas 37% was in PL fractions. For arachidonic acid the reverse was true, 60% of the total uptake was incorporated into PL fractions whereas less than 35% was in TAG. Marked differences were also found in the distribution of the fatty acids into individual phospholipid classes. The higher incorporation of docosahexaenoic acid and arachidonic acid was found in PC and PE, respectively. The greater cellular uptake of docosahexaenoic acid and its preferential incorporation in TAG suggests that both uptake and transport modes of this fatty acid by the placenta to fetus is different from that of arachidonic acid.     

Suppression of arousal by progesterone in fetal sheep

The high rate of progesterone synthesis by the placenta in late gestation exposes the ovine fetus to high concentrations of progesterone and its metabolites that may affect activity of the fetal brain. The aim of this study was to determine the effect of inhibiting maternal progesterone synthesis on sleep-wake activity in fetal sheep. Fetal and maternal vascular catheters, a fetal tracheal catheter, and electrodes for recording fetal electrocortical (ECoG), electro-ocular (EOG) and nuchal muscle electromyographic (EMG) activity were implanted. At 128-131 days gestation, progesterone production was inhibited by an injection of trilostane (50 mg), a 3beta-hydroxysteroid dehydrogenase inhibitor. Vehicle solution or progesterone (3 mg h(-1)) was then infused into the ewe between 6 and 12 h after the trilostane treatment. Maternal progesterone concentrations were significantly reduced from 1-24 h after trilostane treatment (P < 0.05) when followed by vehicle infusion. Fetal breathing movements (FBM), EOG, nuchal muscle EMG, and behavioural arousal increased 12 h after trilostane treatment (P < 0.05). In contrast, there was no change in fetal arousal, EOG, EMG or FBM activities when progesterone was infused after the trilostane treatment. These findings show that progesterone can influence fetal behaviour, and indicates that normal progesterone production tonically suppresses arousal, or wakefulness in the fetus.     

Effects of infused sodium lactate on glucose and energy metabolism in healthy humans

To assess the effects of lactate on glucose metabolism, sodium lactate (20 mumol.kg-1.min-1) was infused into healthy subjects in basal conditions and during application of a hyperinsulinaemic (6 pmol.kg-1.min-1) euglycaemic clamp. Glucose rate of appearance (GRa) and disappearance (GRd) were measured from plasma dilution of infused U- 13C glucose, and glucose oxidation (G(ox)) from breath 13CO2 and plasma 13C glucose. In basal conditions, lactate infusion did not alter G(ox) (8.8 +/- 0.9 vs 9.2 +/- 1.1 mumol.kg-1.min-1), while GRa slightly decreased from 15.2 +/- 0.8 basal to 13.9 +/- 0.9 mumol.kg-1.min-1 after lactate (p < 0.05). During a hyperinsulinaemic clamp, hepatic glucose production was completely suppressed with or without lactate. Lactate decreased G(ox) from 17.1 +/- 0.4 to 13.4 +/- 1.2 mumol.kg-1.min-1 (p < 0.05), whereas GRd was unchanged (39.7 +/- 3.6 vs 45.6 +/- 2.6 mumol.kg-1.min-1. It is concluded that infusion of lactate in basal conditions does not increase GRa or interfere with peripheral glucose oxidation, and that during hyperinsulinaemia lactate decreases glucose oxidation but does not alter hepatic or peripheral insulin sensitivity.     

The effects of a converting enzyme inhibitor (captopril) and angiotensin II on fetal renal function

1. Renal function was studied in chronically catheterized fetal sheep (119-128 days gestation), before and during treatment of the ewe with the angiotensin converting enzyme (ACE) inhibitor, captopril, which crosses the placenta and blocks the fetal renin angiotensin system. 2. An i.v. dose of 15 mg (about 319 micrograms kg-1) of captopril to salt-replete ewes followed by an infusion to the ewe of 6 mg h-1 (about 128 micrograms kg-1 h-1) caused a fall in fetal arterial pressure (P < 0.01), and a rise in fetal renal blood flow (RBF) from 67.9 +/- 5.6 to 84.9 +/- 8.3 ml min-1 (mean +/- s.e. mean) (P < 0.05). Renal vascular resistance and glomerular filtration rate (GFR) fell (P < 0.01); fetal urine flow (P < 0.01); fetal urine flow (P < 0.01) and sodium excretion declined (P < 0.05). 3. Ewes were treated for the next 2 days with 15 mg captopril twice daily. On the 4th day, 15 mg was given to the ewe and fetal renal function studied for 2 h during the infusion of captopril (6 mg h-1) to the ewe. Of the 9 surviving fetuses, 3 were anuric and 3 had low urine flow rates. When 6 micrograms kg-1 h-1 of angiotensin II was infused directly into the fetus RBF fell from 69 +/- 10.1 ml min-1 to 31 +/- 13.9 ml min-1, GFR rose (P < 0.05) and urine flow (P < 0.01) and sodium excretion increased in all fetuses. 4. It is concluded that the small fall in fetal arterial pressure partly contributed to the fall in fetal GFR but in addition, efferent arteriolar tone fell so that the filtration pressure fell further. Thus maintenance of fetal renal function depends on the integrity of the fetal renin angiotensin system. These findings explain why use of ACE inhibitors in human pregnancy is associated with neonatal anuria.     

Fetal supraventricular tachycardia complicated by hydrops fetalis: a role for direct fetal intramuscular therapy

Maternally administered digoxin for the treatment of fetal supraventricular tachycardia (SVT) complicated by hydrops fetalis may be ineffective secondary to poor transplacental drug transfer. We present our experience with eight pregnancies treated with transplacental therapy or combined maternal and direct fetal intramuscular therapy. Response to treatment following maternal intravenous administration (MIV) of digoxin or a combination of fetal intramuscular (FIM) digoxin and MIV is described for eight hydropic fetuses during nine successful pharmacologic conversions. The MIV digoxin was administered using standard loading and maintenance protocols. FIM was administered at a dose of 88 micrograms/kg q 12-24 hours, to a maximum of three injections in the fetal buttock. Time to onset of the first two hours of sinus rhythm (TO2 degrees), time to onset > 90% sinus rhythm (TO > 90%), and time to resolution of hydrops fetalis (HF) were noted. The mean heart rate was 257 +/- 36 beats/minute and the mean gestational age was 29 +/- 4.8 weeks. Fetal SVT was due to a reentrant mechanism in all cases. For the three fetuses that underwent successful cardioversion following MIV digoxin (all required additional maternal antiarrhythmic drugs), TO2 degrees was 145 +/- 114 hours, TO > 90% was 176 +/- 55 hours, and HF resolved in 41 +/- 37 days. Initial combined FIM and MIV therapy in four fetuses resulted in a TO2 degrees of 5.5 +/- 4 hours, TO > 90% of 22 +/- 14 hours, and resolution of HF in 25 +/- 21 days. For the two failed cardioversions with transplacental treatment alone (one fetus had recurrent SVT with hydrops after initial successful cardioversion with MIV), TO2 degrees was 203 +/- 180 hours and TO > 90% was 313 +/- 270 hours. Once FIM was begun in these fetuses, TO2 degrees was 17 +/- 7 hours and TO > 90% was 60 +/- 13 hours; HF resolved in 45 days in one fetus, whereas the other fetus never had resolution of hydrops despite 100 days of antiarrhythmic therapy. Direct fetal intramuscular injection of digoxin combined with transplacental therapy appears to shorten the time to initial conversion of SVT and to sustain sinus rhythm in the fetus with SVT complicated by hydrops fetalis.     

Human placental transfer of the prostaglandin inhibitor sulindac using an in vitro model

OBJECTIVE: We determined whether the prostaglandin inhibitor sulindac crosses the human placenta. METHODS: The recirculating single-cotyledon placenta model was used to characterize the maternal-to-fetal and fetal-to-maternal transport of 14C-labeled sulindac in normal term placentas perfused immediately after delivery. Antipyrine was added as a standard for simple diffusion. Serial samples were taken from both reservoirs during each 3-hour perfusion. Transport was calculated using liquid scintillation spectrometry for 14C-labeled sulindac and high-performance liquid chromatography for antipyrine. RESULTS: There was significant maternal-to-fetal transfer of sulindac. The mean (+/- SD) transfer at 2 hours was 7.22 +/- 2.57%. The fetal-to-maternal transfer was similar at 10.75 +/- 3.80%. The mean maternal/fetal concentration ratio of sulindac was 0.42 at 3 hours. Placental uptake ranged from 24-45 ng/g of placenta. CONCLUSIONS: Sulindac crosses the human placenta in small but significant amounts. The transport is similar in both directions, implying simple diffusion.     

Possible effects of placental leucine aminopeptidase on the regulation of brain-gut hormones in the fetoplacental unit

The hydrolysis of somatostatin by human placental subcellular fractions and pregnancy sera was studied in the presence of selective inhibitors and the antibody against pregnancy serum oxytocinase (placental leucine aminopeptidase; EC3.4.11.3) by measuring the released amino acids by high-performance liquid chromatography. We also studied the degradation of other brain-gut hormones, such as glucagon, growth hormone, growth hormone releasing factor, and insulin, in the human placenta and found that the human placenta degrades somatostatin, glucagon, and growth hormone releasing factor, but not insulin and growth hormone. The degradation velocity of somatostatin was ten times greater than that of growth hormone releasing factor in placental microsomal fractions. Our data suggest that the stimulatory control by growth hormone releasing factor is dominant in the fetal growth hormone secretion. Our data also identified the somatostatin-degrading protease in human placenta using placental leucine aminopeptidase. It is known that the mean somatostatin levels in the umbilical artery are about 2.5-fold higher than those in the umbilical vein. Our data on somatostatin levels in umbilical artery and vein of intrauterine growth retardation human fetuses showed that the ratio umbilical artery/vein is around 1. Since insulin is known to be the primary hormone regulating the ratio of fetal growth, our data suggest that the degradation of somatostatin in the placenta is decreased and that elongation of somatostatin effects may result in the inhibition of insulin secretion in the intrauterine growth retardation fetus.