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M J Novy

Publications and source records attributed to M J Novy.

At least 55 records · Page 3Linked to original sources
PubMed1989

Disparity in the response of sex steroid-binding protein and corticosteroid-binding globulin to thyroxine in the primate.

There is uncertainty regarding the differential effects of thyroid hormone on the circulating levels of sex steroid-binding protein (SBP) and corticosteroid-binding globulin (CBG). Therefore, we studied the effects of elevated thyroxine (T4) on SBP and CBG concentrations in serum in 4 baboon (Papio anubis) infants between 6 and 7 mo of age. The infants were given levothyroxine in increasing doses (25 to 600 micrograms) over a 1-mo period until the peripheral T4 levels were 3-4 times higher than baseline values. Each animal served as its own control. Blood samples were obtained at 2- to 3-day intervals prior to and during treatment. Serum T4 was measured by RIA. SBP and CBG were measured by diethylaminoethyl cellulose filter paper assays. Elevations in serum T4 resulted in a dose-response increase in circulating SBP concentrations with a maximal increase at the 600-micrograms dose of T4 (p less than 0.001). In contrast, significant elevations in peripheral CBG levels occurred with 50 and 100 micrograms of T4 (p less than 0.025 and p less than 0.01, respectively), but decreased thereafter with higher doses of T4. At the 600-micrograms dose of T4, CBG concentrations returned to baseline values. We conclude that in the baboon, T4 increases the circulating levels of SBP in a graded fashion, while the effect on CBG is biphasic.

Animals↗
PubMed1989

Dynamics of steroid biosynthesis during the luteal-placental shift in rhesus monkeys.

We studied the dynamics of steroid secretion during the luteal-placental shift of early pregnancy in rhesus monkeys. Daily blood samples were obtained from six pregnant rhesus monkeys during the cycle of conception and for the first 44 days of pregnancy to examine the relationships among aromatizable androgens, estrogens, progesterone (P), and CG in the peripheral circulation. To elucidate the biosynthetic mechanisms involved in the changes in hormonal patterns, minces of placentae and corpora lutea (CL) were incubated in vitro with [3H]pregnenolone ([3H]P5) and [3H]androstenedione ([3H]A), and steroid metabolites were isolated and identified by reverse isotope dilution. After a brief rise (corresponding to the approximate time of implantation of the blastocyst), serum P levels declined despite rising serum CG levels and reached a nadir at the time of maximal CG secretion. In contrast, serum androstenedione (A), testosterone (T), estrone (E1), and estradiol (E2) concentrations rose and fell in parallel with CG and reached peak levels near day 24 of pregnancy 2- to 10-fold higher than those during the luteal phase. The CL of early pregnancy produced less than one third as much P from [3H]P5 as did the CL of the cycle, but had a 9-fold greater capacity for estrogen biosynthesis. Total CL aromatase activity did not differ between the nonfertile cycle and early pregnancy. 17-Hydroxylase and C17-20 lyase activities increased in the CL during early pregnancy, since 17-hydroxyprogesterone and A (but not T) syntheses were 3- to 5-fold greater in the CL of early pregnancy than in the CL of the cycle. Although serum E1 and E2 concentrations during early pregnancy were similar, E1 was the predominant estrogen produced from [3H]P5 or [3H] A by luteal tissue in vitro. Placental tissue obtained on days 23-27 of pregnancy produced large amounts of P from [3H]P5, but only trace amounts of estrogens were formed from [3H]A. By day 45 of pregnancy, however, the placenta had acquired substantial amounts of aromatase activity. Neither estrogens nor androgens were formed from [3H]P5 by the placenta.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgens↗
PubMed1989

The effect of relaxin infusion on prolactin and growth hormone secretion in monkeys.

To test the hypothesis that relaxin may affect pituitary hormone secretion, synthetic human relaxin was infused into cycling and pregnant rhesus monkeys. Doses ranging from 0.154-1540 ng/kg.min were calculated to achieve circulating relaxin concentrations of 1 pM to 10 nM. Low (0.154 and 1.54 ng/kg.min), intermediate (15.4 and 154 ng/kg.min), and high (1540 ng/kg.min) doses of relaxin were infused for 15 min each hour into ovulating monkeys at the midluteal phase of the menstrual cycle in two separate experiments. Serum GH and PRL were measured by RIA, and serum relaxin was determined by enzyme-linked immunosorbent assay. Relaxin was undetectable in peripheral plasma during the control saline infusion and during infusion of the lowest dose of relaxin. Serum relaxin levels reached 0.011, 0.119, 0.965, and 13.0 nM with 1.54, 15.4, 154, and 1540 ng/kg.min, respectively. Serum GH was significantly elevated over basal levels upon infusion of relaxin from 1.54-1540 ng/kg.min; however, a plateau was observed with the intermediate doses, and a decrease in the magnitude of the response was observed at the highest dose. Serum PRL increased over basal levels with 15.4 and 154 ng/kg.min, but there was no difference in the magnitude of the increase between these doses. PRL levels during infusion of the highest dose of relaxin were similar to control levels. These data suggest that relaxin can stimulate secretion of GH and PRL in cycling monkeys within a defined dose range, but that a decrease in pituitary responsiveness occurs at higher doses. One high dose of relaxin (2600 ng/kg.min) was infused for 1 h into the maternal and then the fetal circulations of chronically catheterized and tethered pregnant monkeys between 120-140 days gestation. Upon infusion of relaxin into the maternal circulation, there was a significant elevation of PRL in the mother but not the fetus. Upon infusion of relaxin into the fetus, there was no consistent change in PRL secretion in either the mother or the fetus. In conclusion, relaxin may have a heretofore undescribed role in pituitary physiology during the menstrual cycle and in pregnancy.

Animals↗
PubMed1988

Intraluteal infusion of a prostaglandin synthesis inhibitor, sodium meclofenamate, causes premature luteolysis in rhesus monkeys.

The physiological significance of locally produced prostaglandins (PGs) in the regulation of the functional lifespan of the primate corpus luteum is unknown. In the current study, the PG synthesis inhibitor sodium meclofenamate was administered to adult female rhesus monkeys beginning in the midluteal phase of the menstrual cycle. Meclofenamate was infused continuously for 7 days into the corpus luteum (100 micrograms/h, n = 6) or the jugular vein (100 micrograms/h, n = 3; 1000 micrograms/h, n = 3) via osmotic minipump. As controls, PBS was infused into the corpus luteum (n = 7) or jugular vein (n = 5). In some of the monkeys receiving intraluteal infusions, chronic aortic and utero-ovarian venous catheters were implanted, and blood samples were collected on alternate days for the measurement of PGE and PGF2 alpha by RIA. Saphenous venous blood was collected daily, and progesterone and cortisol levels were determined by RIA. LH levels were determined by the mouse Leydig cell bioassay. Progesterone levels over 5 days preceding treatment were not different among groups. A decline in progesterone levels on day 1 after surgery was observed in all treatment groups and was accompanied by a 1-day elevation in cortisol levels. Thereafter, five of seven monkeys who received intraluteal infusions of PBS displayed normal progesterone patterns during treatment and normal luteal phase lengths of 15.4 +/- 1.2 days (mean +/- SEM). In six monkeys that received intraluteal infusions of meclofenamate, progesterone levels typically fell to less than 1 ng/ml within 72 h after initiation of infusion; progesterone levels during 7 days of intraluteal infusion were significantly lower (P less than 0.01) in meclofenamate- vs. PBS-treated monkeys. Meclofenamate infusion into the corpus luteum significantly shortened (P less than 0.01) the luteal phase to 10.5 +/- 1.0 days. In contrast, progesterone levels during 7 days of meclofenamate infusion into the jugular vein did not differ from those in PBS-treated monkeys, and the length of the luteal phase was unaltered. LH levels, measured daily, did not differ among groups either before or during treatment. Although an venous/arterial gradient in PGE was detected at the time of surgery, we were unable to detect a significant gradient across the ovary in PGE or PGF2 alpha at any time after surgery in monkeys treated with either PBS or meclofenamate. The present data suggest an obligatory luteotropic role for locally produced metabolites of arachidonic acid, but a physiological role for either PGE or PGF2 alpha in regulating the primate corpus luteum remains equivocal.

Animals↗
PubMed1988

Diagnosis of cornual obstruction by transcervical fallopian tube cannulation.

Interstitial fallopian tube obstruction (IFTO) occurs in 15% of hysterosalpingograms (HSG) performed for infertility. Conventional HSG or laparoscopy may not differentiate cornual spasm or other temporary cause from true obstruction. We used transcervical cannulation of the proximal oviduct with a 3-F Teflon catheter and flexible guidewire 0.018 inch (0.043 cm) in diameter under hysteroscopic or fluoroscopic guidance to evaluate IFTO in 28 patients. Fluoroscopic catheterization techniques with selective salpingography demonstrated patency in 84% of obstructed tubes. Hysteroscopic cannulation with direct visualization by laparoscopy or laparotomy was successful in 92%. In one patient, perforation of the isthmus occurred without sequelae. Transcervical coaxial cannulation of the proximal oviduct is an effective method for evaluating cornual obstruction.

Adult↗
PubMed1987

Plasma concentrations of prostaglandin F2 alpha and prostaglandin E2 metabolites after transabdominal and transvaginal cervical cerclage.

Circulating prostaglandin metabolites 13,14-dihydro-15-keto-prostaglandin F2 alpha and the bicyclo derivative of prostaglandin E2 were measured in maternal plasma by radioimmunoassay after transabdominal cervicoisthmic cerclage and after transvaginal cerclage (Shirodkar and McDonald procedures) performed in the first and second trimesters. Statistically significant elevations in prostaglandin E2 metabolite or 13,14-dihydro-15-keto-prostaglandin F2 alpha occurred after transabdominal cervicoisthmic and transvaginal cerclage; they returned to control levels within 6 to 24 hours after surgery and were associated with good fetal outcome. Increases in 13,14-dihydro-15-keto-prostaglandin F2 alpha were proportionately greater than in prostaglandin E2 metabolite. Mean basal levels and the rise in prostaglandin metabolites were not related to cerclage type, trimester of pregnancy, or cervical status (dilatation less than or equal to 3 cm; effacement less than or equal to 60%). Highest basal and postcerclage 13,14-dihydro-15-keto-prostaglandin F2 alpha and prostaglandin E2 metabolite levels were associated with advanced cervical changes, uterine irritability, membrane prolapse or rupture, and premature delivery. Routine administration of prostaglandin synthetase inhibitors is not indicated for transvaginal cerclage or transabdominal cervicoisthmic cerclage; plasma prostaglandin metabolite levels may identify patients not suitable for cerclage.

Adult↗
PubMed1987

Effects of calcium entry blocker (nicardipine) tocolysis in rhesus macaques: fetal plasma concentrations and cardiorespiratory changes.

Tocolytic doses of nicardipine, a dihydropyridine calcium entry blocker, were administered to chronically catheterized rhesus monkeys between days 128 and 132 of gestation. During periods of spontaneous uterine contractility, a 500 micrograms nicardipine bolus was injected intravenously, and this was followed by continuous infusion (6 micrograms/kg/min) to the mother for 1 hour. Uterine activity (amniotic fluid pressure) and maternal heart rate and blood pressure were monitored continuously. Paired maternal and fetal blood samples were drawn at frequent intervals to monitor pH, PO2, PCO2, and plasma nicardipine concentrations. Peak maternal nicardipine concentrations ranged from 175 to 865 ng/ml while peak fetal levels ranged from 7 to 35 ng/ml. Fetal heart rate and blood pressure were unaffected. However, fetuses became acidotic (pH 7.26 +/- 0.01 versus 7.33 +/- 0.01) and hypoxemic (PO2 16.0 +/- 3.2 versus 24.5 +/- 2.0 mm Hg) after maternal nicardipine treatment (p less than 0.01). Despite the fact that maternal nicardipine treatment exerted a significant tocolytic effect, the undesirable fetal side effects are of concern and deserve further investigation.

Animals↗
PubMed1987

Temporal changes in uterine activity and prostaglandin response to RU486 in rhesus macaques in late gestation.

Progesterone withdrawal as a mechanism of parturition in primates is controversial because maternal, fetal, and amniotic fluid progesterone concentrations do not decrease before parturition. We therefore studied the effects of RU486 on uterine activity and amniotic fluid prostaglandins in four rhesus macaques implanted with amniotic fluid and maternal vascular catheters and with fetal electrocardiogram and uterine electromyogram electrodes at 119 to 124 days' gestation (term = 168 days). Uterine electromyogram, intra-amniotic pressure (hourly contraction area, mm Hg.sec/hr), and fetal electrocardiogram were monitored continuously. After a stabilization period (6 to 9 days) RU486 was administered orally (20 mg/kg/day) at 1000 hours for 3 days. Uterine activity increased from basal levels (less than 4000 mm Hg.sec/hr) 8 hours after the first dose of RU486, reaching levels of 12,000 mm Hg.sec/hr. A sustained increase in uterine activity (13,000 to 30,000 mm Hg.sec/hr) was observed for 48 hours before cesarean section with little or no cervical effacement or dilatation. Increases in amniotic fluid prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, 13,14-dihydro-15-keto-prostaglandin F2 alpha, and 11-deoxy-13,14-dihydro-15-keto-11 beta, 16 epsilon-cycloprostaglandin E2 occurred 40 hours after the onset of increased uterine activity. In contrast, amniotic fluid prostaglandins in the control animals delivering at term (n = 4) increased 24 to 48 hours before significant increases in uterine activity occurred. Control animals but not those given RU486 demonstrated a progressive nocturnal peak in uterine activity before delivery. Progesterone receptor blockade stimulates intense preterm uterine activity but not the orderly sequence of changes in prostaglandins and cervical status observed during normal parturition.

Amniotic Fluid↗
PubMed1987

Rectal infusion of semen results in transient elevation of blood prostaglandins.

Repeated semen deposition in the gut may be linked to the development of viral infections in homosexual men. Other investigators have suggested that rectal insemination may diminish immune responsiveness. We approximated conditions of human insemination by infusing 2 ml of pooled human seminal plasma (SP) into the rectum and/or vagina of rhesus monkeys. This resulted in increased blood plasma concentrations of the bicycloderivative of prostaglandin E (PGEM-II) which reached peak concentrations 2 h after rectal SP instillation in seven of eight test monkeys, but not the controls. The rate of PGE2 diffusion appeared to occur more rapidly across vaginal than rectal mucosa. Suppression of peripheral cellular immune functions was not demonstrated after the single exposure of this study, although persistent and repeat exposures could lead to local or generalized suppression of host defense mechanisms. Absorption of PGE's from the gut may be a cofactor in the development of sexually transmitted viral diseases.

Animals↗
PubMed1987

Fetal responses to altered maternal oxygenation in rhesus monkey.

The purpose of this study was to establish (in the primate) maternal-fetal relations for blood gas parameters and certain related aspects of fetal cardiovascular function with the mother at rest and subjected to a range of altered states of oxygenation. In 10 chronically cannulated rhesus monkey fetuses, with the mother lightly sedated with phencyclidine, on each of two days we studied the effects of maternal hypoxia and hyperoxia [(15, 10, and 100% maternal fractional concentration of inspired O2 (FIO2)] on maternal and fetal pH, PCO2, PO2 and O2 concentration (CaO2) and fetal heart rate, blood pressure, and superior vena caval (SVC) flow distribution. We observed a linear correlation between maternal and fetal pH and PCO2. There was evidence of a fetal metabolic acidosis with 10 but not with 15% hypoxia. Maternal-fetal PO2 and CaO2 correlated in curvilinear and linear fashion, respectively. Maternal-fetal CaO2 difference was maintained within a narrow range (2.7-4.8 vol%) for various states of maternal oxygenation, showing a tendency to expand only with severe (10%) hypoxia. Results indicate that quantitative delivery of O2 to the placenta was of paramount importance as a determinant of O2 transfer to the fetus and are compatible with a "concurrent flow" model of transplacental O2 diffusion. Fetal heart rate decreased progressively with 15 and 10% hypoxia. SVC flow to lungs and placenta varied reciprocally with changes in fetal oxygenation. As indicated by distribution to the heart, shunting of SVC flow through the foramen ovale was modest at rest, with no evident change in response to fetal hypoxemia.

Animals↗
PubMed1987

Modified lamellar body phospholipid assay compared with L/S ratio and phosphatidylglycerol assay for assessment of fetal pulmonary status.

We used a modified lamellar body phospholipid (LB-PL) assay to evaluate the effect of sample processing and to evaluate the clinical efficacy of LB-PL determinations. Within-run and between-run CVs for the modified LB-PL assay respectively ranged from 2.9 to 6.7% and from 3.4 to 14.3%. Freezing and storage at -20 degrees C did not affect results for LB-PL (n = 12). Statistically significant amounts of lamellar bodies were lost on centrifugation, ranging from 20% at 150 X g to 54% at 1000 X g for 5 min. The LB-PL content, lecithin/sphingomyelin ratio, and phosphatidylglycerol content of 194 samples of amniotic fluid obtained within three days of delivery were compared for the assessment of fetal pulmonary maturity. Twenty-three neonates developed respiratory problems at or shortly after birth. With uncontaminated samples (n = 160), the LB-PL assay exhibited better specificity than the lecithin/sphingomyelin ratio (p less than 0.01, Chi square) or the phosphatidylglycerol assay (p less than 0.001, Chi square) for samples obtained after 36 weeks of gestation. Assay sensitivities did not differ significantly. Differences among assay predictive values were not significant.

Amniotic Fluid↗
PubMed1986

Maternal estradiol response to alterations in uteroplacental blood flow.

Low levels of maternal estrogens are commonly regarded as indicators of fetal stress. We continuously monitored distal aortic blood flow by flowmeter, fetal heart rate, and amniotic fluid pressure in seven pregnant baboons near term. Four of the animals received a constant intravenous infusion of [7-3H]dehydroepiandrosterone and [4-14C]estradiol for 270 minutes. A 50% reduction in mean distal aortic blood flow was imposed after 60 minutes by means of partial occlusion of the aorta with a snare device and released at 180 minutes. Blood was collected at 10-minute intervals from 30 to 60 minutes, 120 to 180 minutes, and 240 to 270 minutes. Concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate, estradiol, and cortisol in maternal plasma were determined by radioimmunoassay. Metabolic clearance rates of dehydroepiandrosterone and estradiol were calculated from plasma concentrations of [3H]dehydroepiandrosterone and [14C]estradiol. There was no significant change in maternal levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, or cortisol with alterations in distal aortic blood flow. Three animals exhibited no fetal heart rate evidence of fetal stress; estradiol levels declined during occlusion and returned toward control after release of the snare. Four animals exhibited repetitive late decelerations under conditions of reduced flow; estradiol was unchanged or rose slightly during occlusion but increased three- to 10-fold after release whereas the metabolic clearance rate of both dehydroepiandrosterone and estradiol remained stable. We conclude that placental hypoperfusion without fetal stress results in decreased conversion of aromatizable substrate and elevated maternal estradiol levels during acute hypoxemic fetal stress probably represent increased production of fetal androgen.

Animals↗
PubMed1986

Alterations in sex steroid-binding protein (SBP), corticosteroid-binding globulin (CBG), and steroid hormone concentrations during pregnancy in rhesus macaques.

Temporal relationships between concentrations of sex steroid-binding protein (SBP), corticosteroid-binding globulin (CBG), total and free estradiol, total and free testosterone, cortisol, and progesterone were studied in plasma obtained at 1- to 3-day intervals throughout gestation in six rhesus macaques. Concentrations of SBP and CBG were measured by diethylaminoethyl cellulose filter assays. Total and free steroids were estimated by radioimmunoassay and ultrafiltration dialysis, respectively. We found that SBP was elevated between days 30 and 50 and CBG between days 60 and 140; both then declined until term (167 days). Estradiol increased gradually throughout gestation. Testosterone was elevated between days 10 and 40, then declined, and rose slightly in late gestation until approximately 15 days before delivery, when it increased markedly. Free estradiol and testosterone increased dramatically before parturition. Progesterone was elevated between days 25 and 45 and declined to relatively constant levels thereafter. Cortisol was essentially unchanged throughout gestation. Our data show that in the pregnant rhesus, levels of SBP and CBG vary independently of one another, but both decline before term; concentrations of both total and free estradiol and testosterone increase markedly before parturition; in late gestation, elevated estrogen is not associated with increased levels of SBP or CBG (as it is in human females).

Animals↗
PubMed1985

Relationship of uteroplacental blood flow to placental clearance of maternal plasma C-19 steroids: evaluation of mathematical models.

The concept that the placental clearance of maternal plasma dehydroepiandrosterone sulfate through estradiol formation is a function of uteroplacental blood flow in women has been disputed. We obtained data on the clearance of maternal plasma dehydroepiandrosterone through placental estradiol formation in the baboon and used these data to evaluate some mathematical models of placental clearance. Our evaluation shows that the placental clearance of dehydroepiandrosterone is proportional to uteroplacental blood flow in the baboon.

Animals↗
PubMed1985

Effect of dexamethasone treatment on sex steroid-binding protein, corticosteroid-binding globulin, and steroid hormones in cycling rhesus macaques.

We tested the hypothesis that dexamethasone lowers sex steroid-binding protein levels and observed the effect of dexamethasone on corticosteroid-binding globulin and specific steroid hormones in plasma. Four cycling rhesus macaques were studied during three consecutive menstrual cycles (first and third cycles served as controls). In the second cycle, each animal received 0.5 mg of dexamethasone intramuscularly at 8:00 AM and 8:00 PM daily for 21 consecutive days. Blood samples were taken at 1- to 3-day intervals during each cycle. Concentrations of sex steroid-binding protein, corticosteroid-binding globulin, cortisol, testosterone, progesterone, and estradiol were measured in plasma. The percentage and plasma concentration of free testosterone were also determined. Within 2 days of treatment, dexamethasone suppressed cortisol to 5% of baseline values, which returned in the third cycle. All cycles were ovulatory. Dexamethasone significantly lowered plasma levels of all the compounds except progesterone: sex steroid-binding protein, -30%; corticosteroid-binding globulin, -14%; testosterone, -36%; and estradiol, -45%. The percentage of free testosterone was significantly elevated, but free testosterone concentrations were unchanged. Although our data conclusively show that dexamethasone suppresses plasma sex steroid-binding protein levels in the rhesus macaque, it remains to be established whether this suppressive effect leads to an increase in the metabolic clearance rate of testosterone.

Animals↗
PubMed1985

Direct effect of sex steroid-binding protein (SBP) of plasma on the metabolic clearance rate of testosterone in the rhesus macaque.

We report direct evidence for the effect of the sex steroid-binding protein (SBP) on the metabolic clearance rate of testosterone (MCRT). Pure rhesus SBP or human SBP was infused intravenously into three different cycling female rhesus monkeys. MCRT was measured before and after SBP had reached 150-300% of basal levels. A decrease in MCRT was observed in all cases. The effect of SBP on MCRT was tested further in four additional cycling females by infusing immunoaffinity-purified monospecific human SBP antibodies known to cross-react with rhesus SBP. SBP dropped to 54, 40, 4 and 2% of basal levels with a concomitant increase of 118, 190, 320 and 640% of basal MCRT. In one of these animals, pure rabbit SBP was administered after the anti-human SBP infusion resulting in a decrease in MCRT. The magnitude of the SBP effect on MCRT is related to the distribution of testosterone (T) bound to SBP and albumin in the plasma. Calculations show that as long as the percent of T bound to SBP is equal or higher than the percent of T bound to albumin, the influence on MCRT is small. However, if SBP is reduced to the extent that T is bound mostly to albumin, the redistribution of T is associated with a dramatic increase in MCRT. We conclude that under normal conditions each animal has an optimum concentration of plasma SBP which binds a maximum amount of T. If SBP increases above this level, little effect on MCRT will result. However, a drop below the optimum level, as is the case in certain physiological or clinical conditions, will produce a large increase in the clearance of T.

Animals↗
PubMed1985

Maternal and fetal production rates of progesterone in rhesus macaques: placental transfer and conversion to cortisol.

Maternal and fetal progesterone (P4) metabolism and placental transfer were examined in vivo. Via a femoral vein, 3.2 microCi[14C]P4 were infused at a constant rate for 2 h into five rhesus macaques on days 131-137 of gestation. Simultaneously, 12 microCi[3H]P4 were infused into the fetuses via a placental bridging vein. Measurement of steady state concentrations of [14C]- and [3H]P4 in the maternal and fetal circulations permitted calculation of the MCRs, production rates (PRs), and transfer rates (Vs) of P4. The maternal MCR (533 liters/day) was higher than the fetal MCR (93 liters/day), whereas the maternal PR did not differ significantly from the fetal PR (2.3 and 1.0 mg/day, respectively). Placental transfer of P4 from the fetal to maternal circulation (VFM) was greater than that from the maternal to fetal circulation (VMF). Values were 0.23 and 0.07 mg/day, respectively. The utilization of circulating P4 as a substrate for fetal cortisol (F) production was examined in three additional monkeys for whom the amount of isotopically labeled P4 infusate was increased 5-fold. By determining the ratio of specific activities of [3H]F and [3H]P4 in the fetal circulation, we found the maximum contribution of circulating fetal P4 as a precursor of fetal F to be less than 1%. Our results indicate that: 1) higher fetal than maternal plasma P4 concentrations (11.3 and 4.3 ng/ml, respectively) are most likely the result of 5-fold lower fetal MCR, since the PRs are similar in the fetal and maternal compartments, and the VFM is greater than the VMF; and 2) fetal F production using circulating P4 as a substrate is minimal.

Animals↗