Iron content and molecular weight of uteroferrin and a comparison of its iron and copper forms.

The molecular weight of the purple, iron-containing glycoprotein uteroferrin has been determined to be 35140 +/- 1610 by sedimentation equilibrium centrifugation. This is consistent with measurements carried out by other procedures. The dry weight of a solution of uteroferrin with an absorption of 1.00 cm -1 at 280 nm was 0.87 mg/ml. Highly purified uteroferrin has a ratio of absorbance at 280 nm to 545 nm of about 13.2 and a revised extinction coefficient at 545 nm of 3.1 . 10(3) M -1 is presented. The iron content of uteroferrin has been determined both colorimetrically and by atomic absorption spectroscopy. One iron atom is present per polypeptide chain. Reduction with dithionite leads to loss of iron, allowing the apoprotein to be prepared. Enzymatic activity can be restored to the apoprotein with Fe(III) or with Cu(II). The copper enzyme has no visible color and has a higher pH optimum than the Fe-uteroferrin. Whereas the phosphatase activity of the latter is increased several-fold by beta-mercaptoethanol, reduction inactivates Cu-uteroferrin. Both forms of uteroferrin have similar Km values for p--nitrophenyl phosphate and are inhibited by molybdate but not by tartrate. Excess Cu(II) and Fe(III) strongly inhibit uteroferrin phosphatase activity and these results may explain the failure of other to restore activity to the apoprotein using Cu(II) and Fe(III) salts.

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.

Effect of constant light on fetal and maternal prolactin rhythms in sheep.

A 24-h rhythm of plasma PRL is present in fetal sheep. This rhythm is synchronized to an environmental clue (zeitgeber). We determined whether the light-dark cycle (L:D) is a zeitgeber for the fetal PRL rhythm and, if so, whether the mother might convey this zeitgeber to the fetus. We kept nine ewes (twin pregnancies) in constant light (L:L) and five ewes (singleton) in 14:10 L:D from 110 days gestation. Fetuses and mothers were catheterized at 119 days gestation. Blood samples were taken hourly for 24 h after 16 days under L:L or L:D. A mean 24-h rhythm of PRL was found (by RIA) in fetuses under L:D, but not in those under L:L. However, fetuses under L:L showed individual 24-h PRL rhythms (cosinor analysis) whose acrophases were distributed around the clock. Nonsynchronized rhythms persisted after 23 and 30 days of L:L. Acrophases of PRL rhythms within a set of twins were closer than those between sets, suggesting that twins were responding to a common signal. These findings indicate that the L:D cycle is a zeitgeber for the PRL rhythm in fetal sheep and suggest that the mother might convey the zeitgeber.

Endocrine and morphological maturation of the fetal and neonatal adrenal cortex in baboons.

Developmental changes in basal and circadian fluctuations in plasma dehydroepiandrosterone sulfate (DHEAS) and cortisol (F) from birth until 3 months of life were studied in conjunction with morphological characteristics of the fetal and neonatal adrenal cortex in baboons (Papio anubis). These studies were complimented by measurements of in vitro production of DHEAS and F (basal and ACTH stimulated) by adrenal tissue slices. Cortisol, DHEAS, estrone, estradiol, and progesterone were determined in plasma and incubation medium by specific RIA. After delivery, an initial rise in plasma DHEAS was sustained for 4 days, followed by a precipitous decline, which reached a nadir between days 10-12 postpartum. Thereafter, plasma DHEAS and F concentrations stabilized with minor fluctuations. A significant (P less than 0.05) and persistent diurnal rhythm in DHEAS and F secretion was evident by the end of the first week after birth. Administration of estrone acetate and progesterone in oil maintained neonatal plasma concentrations of estrone, estradiol, and progesterone at levels comparable to those in utero, but had no quantitative or qualitative effect on the pattern of plasma DHEAS or F in the neonate. The relative production of F to DHEAS by tissue slices in vitro (the calculated F/DHEAS ratios) indicates that DHEAS secretion by the fetal adrenal is 10-fold higher than that of F near parturition; ACTH stimulation does not alter this relationship. By postnatal day 10, the basal production rates of F and DHEAS are equivalent, and the response to ACTH stimulation favors production of F. With advancing neonatal age (at 30 and 100 days), there is an increase in the F/DHEAS secretion ratio both during the basal state and in response to ACTH. The baboon adrenal glands increased in weight during the last month of gestation and then stabilized during the early postnatal period; a gradual increase in weight was observed after 30 days postpartum. Within 2 weeks after parturition, the relative width of the fetal zone decreased dramatically to occupy less than one third of the total cortex. During involution, we observed a decrease in cell size and a reduction in cytoplasmic vacuolation. A zone of closely packed cells with numerous areas of cell death (the dense band) separated the zona fasciculata from the fetal zone. Cell proliferation was observed in the upper regions of the definitive cortex. We conclude the following. 1) The hypothalamic-hypophyseal mechanisms that regulate the diurnal adrenal secretory rhythm are established in the early neonatal period in the baboon.(ABSTRACT TRUNCATED AT 400 WORDS)

A function of the allantoic sac in the metabolism of uteroferrin and maternal iron by the fetal pig.

The possible roles of the allantoic sac in metabolism of uteroferrin, the iron-containing, purple phosphatase, were examined. This protein, which originates in the maternal endometrium, was measured in allantoic fluid by a specific double-antibody radioimmunoassay and by its beta-mercaptoethanol-activated acid phosphatase activity. Total uteroferrin reaches a maximum between days 60 and 75 of pregnancy, when it constitutes up to one-third of the total protein, and then declines towards term. Fluid volume, total protein and total iron also reach a maximum around day 60. Two-dimensional polyacrylamide-gel electrophoresis was employed to identify proteins in allantoic fluid. Of the proteins detected, at least three basic and two acidic polypeptides are also characteristic of maternal uterine secretions. The remaining proteins appeared identical to those found in fetal serum and included transferrin, albumin and alpha-fetoprotein. Although uteroferrin acid phosphatase activity is stable when incubated in buffer, the enzyme loses activity in sterile allantoic fluid collected at all stages of pregnancy. Experiments with 59Fe-uteroferrin have shown that allantoic fluid promotes iron loss from uteroferrin and that the metal appears in transferrin. Thus the allantoic sac may serve not only as a depot for uteroferrin accumulation but as a site of active iron metabolism.

Functional determination of oxytocin affinity in near-term pregnant rat myometrium: effect of chronic hypoxia.

We designed the present study to determine: (1) if phenoxybenzamine can be used as an irreversible blocker for oxytocin receptors, and as such to determine oxytocin affinity, (2) if prolonged hypoxic exposure alters oxytocin receptor coupling efficacy of oxytocin receptors to post-receptor mediated mechanisms in the rat myometrium. Rats were exposed to room air (control), or to continuous hypoxia (10.5% O2) from day 19 through day 21 (2-day exposure). On day 21, one uterine horn was removed and used for in vitro study of myometrial contractile responses to oxytocin, while the other was used for oxytocin receptor analysis. In normoxic tissues, phenoxybenzamine (20 microM) decreased the maximum contractile response (EMAX) to oxytocin (155+/-17 vs. 66+/-19 g s/cm2) and oxytocin binding sites (BMAX: 253+/-35 vs. 114.9+/-21.3 fmol/mg protein). A similar degree of reduction in EMAX and BMAX were observed in hypoxic tissues. The oxytocin dissociation constant (KA) in the normoxic rat was 2.8+/-0.7 nM, which was not different from the chronic hypoxic rat (3.3+/-0.9 nM). Analysis of receptor occupancy-response curves indicated no oxytocin receptor reserve in both normoxic and hypoxic myometrium. However, for a given fraction of the total oxytocin receptors occupied, hypoxic tissue elicited a lower contractile response to oxytocin. We conclude that: (1) phenoxybenzamine is a useful tool to functionally study oxytocin receptor kinetics, (2) prolonged hypoxic exposure does not affect the oxytocin affinity, (3) no spare receptors for oxytocin are present in the rat myometrium, and (4) prolonged exposure to hypoxia decreases oxytocin receptor-effector coupling efficiency in rat myometrium.

Chronic hypoxia and developmental regulation of cytochrome c expression in rats.

OBJECTIVE: To test the hypothesis that chronic hypoxia upregulates cytochrome c expression in heart, brain, and liver of fetal and maternal rats. METHODS: Time-dated pregnant Sprague-Dawley rats were divided into normoxic and hypoxic (48 hours of 10.5% oxygen from days 19 to 21) groups, and were killed on day 21. Tissue levels of cytochrome c in heart, brain, and liver were determined by using monoclonal antiserum for cytochrome c. RESULTS: Chronic hypoxia caused a decrease in fetal body weight (5.3 +/- 0.1 to 4.7 +/- 0.1 g) and an increase in heart/body weight ratio (0.0048 +/- 0.0001 to 0.0061 +/- 0.0002). Cytochrome c levels were 4-, 2.6-, and 13-fold higher in heart, liver, and brain, respectively, of the mother than of the fetus. Chronic hypoxia did not change cytochrome c levels in maternal tissues but caused a 70% increase and 54% decrease in cytochrome c levels in the fetal heart and liver, respectively. No difference was observed in the fetal brain. CONCLUSIONS: The results suggest that expression of cytochrome c is tissue specific and developmentally regulated. Chronic hypoxia showed differential regulation of cytochrome c levels both developmentally and tissue specifically. The increased sensitivity of cytochrome c in fetal tissue to chronic hypoxia is likely to represent a fetal adaptive mechanism to the stress of chronic hypoxia.

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.

Role of uteroferrin in placental iron transport: effect of maternal iron treatment on fetal iron and uteroferrin content and neonatal hemoglobin.

Uteroferrin, an Fe-containing, progesterone-induced glycoprotein is involved in maternal to fetal Fe transport in swine. These studies examined the effect of im Fe injection of dam on conceptus and piglet Fe stores. In Exp. I, eight gilts were bred and assigned to either treatment I (no Fe injections) or treatment II (total of 22 mg iron-dextran/kg body weight on d 40, 45, 50, 55 and 60 of gestation) and hysterectomized on d 90 to determine whether Fe injections increased Fe stores in the conceptus. Total Fe in allantoic fluid (P less than .10) as well as uteroferrin concentration (P less than .05) and total uteroferrin (P less than .05) in placentae were greater for gilts in treatment II. In Exp. II, 19 cross-bred sows were bred and assigned to treatments I and II (d 40, 50 and 60 of gestation), as in Exp. I, and treatment III (total of 22 mg iron-dextran/kg body weight on d 90, 100 and 110 of gestation) to determine effects of treatment on hemoglobin (Hb) values of the piglets at 8 +/- 1 h and d 4 postpartum. Piglets from treatment II had higher (P less than .01) Hb at 8 +/- 1 h, but not on d 4 postpartum. Experiment III was a replication of Exp. II except that Hb values were determined at 8 +/- 1 h, d 4 and d 7 postpartum. On d 7, piglets from treatment II had higher (P less than .05) Hb, but differences at 8 +/- 1 h and d 4 were not significant (P greater than .10).(ABSTRACT TRUNCATED AT 250 WORDS)

Nucleic acid, metabolic and histological changes in gilt mammary tissue during pregnancy and lactogenesis.

Changes in mammary gland histology, dry weights, nucleic acids and in vitro rates of substrate oxidation in incorporation into lipid were measured in mammary biopsies of three gilts each on d 30, 45, 60, 75, 90, 105 and 112 of pregnancy, and d 1 and 4 of lactation. Histological changes noted were progressive duct growth early in pregnancy followed by rapid lobulo-alveolar development between d 75 and 90 to complete mammogenesis. Colostrum and lipid were evident by d 105 with marked distension of alveolar lumina on d 112. Complete differentiation of the secretory process was apparent on the day of parturition. Concentrtion of dry, fat-free tissue (DFFT) and DNA changed little before d 60 but increased fourfold between d 75 and 90. No further increases in DFFT or DNA were noted. RNA concentrations paralleled DNA through d 90, after which they steadily increased. Rates of acetate and glucose oxidation increased transiently during midpregnancy then declined and remained low until initiation of lactogenesis. Substrate incorporation into lipid increased slightly at midpregnancy and again at d 105, after which it increased markedly. Collectively, results indicate that mammogenesis is complete by d 90, after which lactogenesis is initiated in a two-stage process. Metabolic rates expressed on a DNA basis indicated considerable rates of oxidation, but not of lipogenesis by proliferating mammary tissue. Preferential metabolism of acetate vs glucose near parturition suggests coordination of metabolism between the mammary gland and other maternal tissues.

Role of uteroferrin in placental iron transport in swine: relationship between uteroferrin levels and iron deposition in the conceptus during gestation.

This study was to examine the relationship between uteroferrin and Fe, and Fe and Cu in the fetal pig. In Exp. 1, conceptus tissues and fluids were obtained on d 30, 45, 60, 75 and 90 of gestation for Fe and Cu analyses. In fetus minus liver, total Fe and Cu increased constantly between d 30 and 90, but Fe and Cu concentrations (microgram/g dry tissue) both decreased between d 30 and 45 and then remained relatively constant to d 90. For fetal liver, total Fe increased from d 30 (27 micrograms) to d 90 (3,222 micrograms), as did total Cu (14 micrograms on d 30 to 960 micrograms on d 90). Fetal liver Fe concentration (microgram/g dry tissue) decreased from d 30 (1,021) to d 60 (472) and then increased to d 90 (1,082), whereas Cu concentration increased between d 30 (537) and 60 (830) and then decreased between d 60 (471) and 90 (329). In allantoic fluid, both total Fe and Cu increased between d 30 and 60 and then decreased to d 90. Data from this study indicated a close temporal relationship between Fe and Cu in the fetal tissues and fluids examined. In Exp. 2, the relationship between Fe and uteroferrin in fetal tissues and fluids was studied. Uteroferrin, measured indirectly by acid phosphatase activity and Fe in fetal tissues and fluid underwent closely related temporal changes between d 30 and 112 of gestation. Changes in total Fe and Fe concentration during gestation were similar to those described for Exp. 1 in fetus minus liver, fetal liver and allantoic fluid. In addition, total Fe and Fe concentration in placental and endometrial tissues were analyzed. It was concluded that uteroferrin provides a major source of Fe in endometrial secretion and that it may be stored in placental and endometrial tissues. The relationship between Fe and Cu in conceptus tissues and erythropoiesis also is discussed.

Fetal and maternal adaptations to chronic hypoxia: prevention of premature labor in response to chronic stress.

Both mother and fetus have the remarkable ability to adapt to conditions of chronic hypoxia during the course of gestation. One of these adaptations appears to be mechanisms that prevent premature delivery despite the chronic stress of hypoxia. Our studies in the chronically hypoxic sheep revealed that the fetal adrenal is less responsive to ACTH stimulation. This in turn may prevent a premature rise in cortisol that would normally trigger labor and delivery. In the rat, the myometrium is affected with a decrease in contractile sensitivity to oxytocin following chronic hypoxia. This response is mediated by a significant reduction in myometrial oxytocin receptors. Our preliminary studies have also suggested that this blunting of myometrial responsiveness also occurs in the chronically hypoxic sheep. Taken together, these data indicate an adaptive response by both mother and fetus to prevent preterm delivery in the face of a chronic stress.

Circadian uterine activity in the pregnant rhesus macaque: do prostaglandins play a role?

Eight rhesus macaques between 127 and 132 days of gestation had catheters implanted into maternal femoral vessels and the amniotic fluid cavity and were placed in a vest-and-tether system for chronic catheter maintenance. Uterine activity was continuously recorded, and paired maternal arterial blood and amniotic fluid samples were collected at 0900 h (AM) and 2100 h (PM) until delivery and analyzed for prostaglandin metabolites (PGFM and PGEM-II). A circadian pattern in uterine contractility was observed, with peak activity occurring between 1900 and 0100 h (p less than 0.001). No significant AM-PM differences were observed in maternal plasma PGFM (240 +/- 24 AM vs. 273 +/- 35 PM) or PGEM-II (537 +/- 41 AM vs. 484 +/- 34 PM) or amniotic fluid PGFM (360 +/- 72 AM vs. 287 +/- 70 PM) or PGEM-II (1626 +/- 383 AM vs. 1771 +/- 431 PM). All values represent mean +/- SEM, pg/ml. Additional samples were collected at 3-h intervals for 24 h at selected times during the study. This more intensive sampling protocol also failed to reveal any significant time trends in maternal plasma or amniotic fluid prostaglandins. Despite the lack of AM-PM differences, amniotic fluid PGFM and PGEM-II increased significantly as delivery approached (p less than 0.01). It appears that circadian uterine activity is not related to changes in maternal plasma or amniotic fluid prostaglandins. Although prostaglandins are responsible for the progression of labor, other factors may be involved in the generation of uterine activity rhythms prior to the initiation of labor.

Photoperiod regulation of uterine activity and melatonin rhythms in the pregnant rhesus macaque.

This study tested the hypothesis that photoperiod phase entrains the daily rhythms in myometrial contractility and melatonin in circulation in the pregnant rhesus monkey during late gestation. Six chronically catheterized rhesus macaques were maintained on a 12L: 12D cycle (lights-on, 0700 to 1900 h). Intrauterine pressure was continuously recorded throughout the study. At 120-135 days of gestation, blood samples were collected at 3-h intervals over a 24-h period beginning 2 h after lights-on at 0900 h. We observed a characteristic nocturnal uterine activity rhythm; contractile events peaked at 2300 h compared to the nadir at 0900 h (p less than 0.05, ANOVA). Daytime plasma melatonin levels averaged 31 +/- 6 pg/ml compared to the nocturnal peak of 60 +/- 6 pg/ml at 2400 h (p less than 0.05). Photoperiod was then shifted 11 h so that lights were on from 2000 to 0800 h. After 7 days, blood samples were again collected over 24 h, beginning 2 h after lights-on at 2200 h; this sampling protocol was repeated at weekly intervals until delivery. After 7 days of reversed photoperiod, the peak in the uterine activity shifted to 1100 h, whereas the nadir occurred at 2200 h (p less than 0.05). Melatonin concentrations increased from a mean of 22 +/- 4 pg/ml during the light phase to a nighttime peak of 60 +/- 5 pg/ml at 1300 h (p less than 0.01). A similar and stable phase relationship to lights-off was maintained for both the myometrial activity rhythm and the circadian melatonin rhythms after reversed photoperiod.(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal plasma catecholamines in the rhesus macaque during late gestation: effect of photoperiod and timed melatonin infusion.

This study tested the hypothesis that changes in photoperiod alter plasma catecholamine concentrations in the rhesus monkey during late gestation. Twelve chronically catheterized pregnant rhesus macaques were acclimated to a 12-h photoperiod (lights-on, 0700-1900 h). Under the control L:D cycle, blood samples were collected at 3-h intervals over 24 h for catecholamine analysis. Plasma concentrations (mean +/- SEM, pg/ml) ranged from 678 +/- 90 to 928 +/- 142 for norepinephrine; 230 +/- 22 to 631 +/- 141 for epinephrine; and 282 +/- 70 to 1090 +/- 362 for dopamine. A diurnal rhythm was observed in epinephrine with peak concentrations during lights-on (0900-1800 h; p less than 0.05, compared to lights-off). After the first sampling protocol, the animals were divided equally between two groups: phase shift, in which lights-on was shifted 11 h (2000-0800 h) and constant light, with lights on continuously. After the phase shift, a parallel shift in the plasma epinephrine rhythm was noted, with peak levels observed between 2200 and 0700 h (p less than 0.05). Constant light abolished the rhythm in epinephrine, with an overall reduction in mean basal levels of all three catecholamines. Daily melatonin infusions (0.2 micrograms/kg/h, 1900-0630 h) under constant light failed to restore the epinephrine rhythm or to return basal catecholamine concentrations to control photoperiod levels. These data suggest that photoperiod entrains the rhythm in epinephrine secretion, but the rhythm is ablated under constant conditions. Further, melatonin does not appear to play a role in the regulation of catecholamine secretion in the pregnant rhesus macaque.

Catecholamines and uterine activity rhythms in the pregnant rhesus macaque.

This study was designed to examine the relationship between uterine contractile rhythms with maternal plasma and amniotic fluid catecholamine concentrations in the pregnant rhesus macaque. Six chronically catheterized rhesus macaques were maintained in a vest and tether system and exposed to a 12L:12D cycle. Continuous uterine activity recordings demonstrated a contractile pattern with peak activity at 2200 h (p less than 0.05). Paired maternal plasma and amniotic fluid samples were collected at 3-h intervals for 24 h between Days 131 and 148 of gestation. Samples were analyzed for norepinephrine, epinephrine, and dopamine by HPLC. Maximum plasma concentrations across the 24-h periods for norepinephrine (633 +/- 230; mean pg/ml +/- SEM) and dopamine (378 +/- 110) were observed at 2100 h and epinephrine (408 +/- 95) at 1200 h, but these values were not significant. The maximum amniotic fluid values were 378 +/- 126, 267 +/- 190, and 556 +/- 87 pg/ml for norepinephrine, epinephrine and dopamine, respectively. However, concentrations across 24 h did not differ. Neither maternal plasma nor amniotic fluid catecholamine concentrations were correlated with uterine activity rhythms. Therefore, we conclude that the nocturnal uterine activity in the rhesus macaque is not related to maternal arterial or amniotic fluid catecholamine concentrations.

Is uterine blood flow controlled locally or systemically in the pregnant rabbit?

OBJECTIVE: We tested the hypothesis that uterine blood flow is regulated by systemic circulating factors. The alternative hypothesis is that uterine blood flow is regulated by local factors. STUDY DESIGN: Adult female New Zealand White rabbits were subjected to a unilateral tubal ligation and thereafter allowed to become pregnant (n = 9). A group of nonpregnant one-tube-ligated animals served as controls (n = 8). On day 21 of gestation uterine blood flow in the pregnant and nonpregnant uterine horns were measured with 15 microns microspheres. The concentration of prostaglandin E2 metabolites were measured in blood from the uterine veins and from the arterial circulation. RESULTS: Absolute uterine blood flow in the pregnant uterine horn was 12.9 +/- 4.7 versus 5.2 +/- 1.4 ml in the nonpregnant horn (p < 0.05). However, when expressed by blood flow per gram of tissue they were not different (p > 0.1). The uterine blood flow for the nonpregnant uterine horn in the pregnant animals was the same as that of the horns from nonpregnant animals. The level of prostaglandin E metabolites was greater in the uterine vein draining the pregnant horn compared to the nonpregnant horn (p < 0.05). CONCLUSION: These data support the conclusion that the increase in uterine blood flow observed during pregnancy is controlled largely by local factors induced by pregnancy.

Cardiovascular responses to adenosine in fetal sheep: autonomic blockade.

The mechanism by which adenosine increases heart rate was investigated in 21 chronically catheterized fetal sheep (> 0.8 term). Intra-arterial infusion of adenosine (0.16 mg.min-1.kg fetal wt-1) for 1 h significantly increased fetal heart rate within 5 min with maximum values of approximately 68 beats/min above the control mean of 163 +/- 8 beats/min. The average diastolic blood pressure was reduced only during the first 10 min of infusion, and the average systolic and mean arterial pressures were not significantly affected. Mean venous pressure rose by approximately 48% after 20 min of adenosine infusion, but all other measurements did not differ significantly from the control value. The mean hemoglobin concentration during the last 30 min of infusion was increased by approximately 8%. Plasma concentrations of norepinephrine and epinephrine were elevated only during the first 30 min of adenosine administration, to values as high as 2.3 and 5 times the respective control mean. Adenosine significantly increased mean fetal heart rate by about 15-20 beats/min in fetuses with autonomic ganglion blockade or combined cholinergic, alpha-, and beta-adrenergic receptor blockade. Intra-arterial infusion of CGS 21680C, an A2-adenosine receptor agonist, also produced a fetal tachycardia of approximately 86 beats/min above the control mean and increased intrinsic fetal heart rate by approximately 38 beats/min. It is concluded that approximately 75% of the positive chronotropic effects of adenosine are produced by A2-receptor stimulation of the autonomic nervous system and that approximately 25% of the rise in heart rate induced by adenosine may be caused by activation of A2-receptors in myocardium.

Circadian hormonal interactions among the mother, fetus, and amniotic fluid.

Circadian rhythms and hormonal interactions among the maternal, fetal, and amniotic fluid compartments were studied in long-term catheterized rhesus macaque monkeys between days 127 and 138 of gestation (term = 167 days). Blood samples were collected at 3-hour intervals for 48 hours and analyzed by radioimmunoassay for estrone, estradiol, cortisol, progesterone, dehydroepiandrosterone sulfate, and prolactin. Distinct circadian rhythms were present for cortisol and progesterone in the maternal circulation and for progesterone and dehydroepiandrosterone sulfate in the fetal circulation (p less than 0.05). Although maternal and fetal estrogen levels were higher in AM samples than in PM samples, a statistically significant circadian rhythm was not present (p greater than 0.10). Fetal levels of progesterone and dehydroepiandrosterone sulfate and maternal levels of progesterone were highest between 9:00 PM and 3:00 AM and lowest between 9:00 AM and 3:00 PM. Maternal levels of cortisol were highest between 6:00 AM and 9:00 AM and lowest between 6:00 PM and 12 midnight. The circadian patterns of maternal cortisol and progesterone were inversely related to each other (r = -0.68; p less than 0.01). Amniotic fluid cortisol levels were highest between 9:00 AM and 12 noon and lowest between 6:00 PM and 3:00 AM (p less than 0.10). With the possible exception of cortisol, amniotic fluid steroid hormones did not demonstrate distinct diurnal fluctuations, nor did they correlate with steroid changes in maternal or fetal blood. Because the rhesus placenta is permeable to glucocorticoids it is likely that transplacental passage of maternal cortisol influences the activity of the fetal pituitary and adrenal so that the circadian rhythm in the fetal axis is 180 degrees out of phase with that of the maternal axis. The circadian rhythms in fetal dehydroepiandrosterone sulfate and progesterone in late gestation parallel the biorhythm in uterine contraction frequency and amplitude, with peaks during periods of darkness between 9:00 PM and 3:00 AM.