beta-endorphin and Fetal-Hypoxia

Perinatal asphyxia is one of the major causes of cerebral injury in neonates. It may be due to the increased endogenous opioid-like substances (OLS) in the body. The levels of three OLS, namely leucine-enkephalin (LEK), beta-endorphin (beta-EP) and dynorphin A1-13 (DynoA1-13) of 44 cases with neonatal asphyxia were studied by radioimmunoassay. The OLS level in plasma and cerebral spinal fluid (CSF) were higher in asphyxiated group than those in the control group, especially in asphyxiated cases with fetal distress. The OLS levels of CSF were also higher in cases with cerebral injury than in those without cerebral injury, while the levels of OLS in plasma had no difference in these two groups. The relationship between OLS levels and asphyxia and cerebral injury is also discussed.

Topics: Asphyxia Neonatorum; beta-Endorphin; Cerebral Hemorrhage; Dynorphins; Enkephalin, Leucine; Female; Fetal Hypoxia; Humans; Infant, Newborn; Male; Peptide Fragments; Pregnancy

Topics: Autistic Disorder; beta-Endorphin; Blood Pressure; Female; Fetal Blood; Fetal Hypoxia; Humans; Hydrocortisone; Hypoxanthine; Hypoxanthines; Intellectual Disability; Multivariate Analysis; Pregnancy; Self Mutilation; Stereotyped Behavior; Stress, Physiological

Topics: Adult; beta-Endorphin; Endorphins; Female; Fetal Blood; Fetal Hypoxia; Humans; Infant, Newborn; Labor Stage, Second; Labor, Obstetric; Meperidine; Pregnancy

To characterize the immunological forms of beta-endorphin (beta-EP) in the fetal circulation, total beta-EP immunoactivity [beta-EPi] and N-acetyl beta-EPi were measured in the plasma of chronically catheterized fetal lambs in undisturbed conditions and before, during, and after periods of controlled hypoxia. Measurements of the peptide concentrations in each plasma sample were made by RIA using an antiserum to the midportion of beta-endorphin which cross-reacts with both acetylated and unacetylated forms of the peptide as well as with beta-lipotropin, and a second antiserum which reacts only with acetylated forms of beta-EP. In 25 plasma samples from 12 fetal animals at 113-142 days gestation, total beta-EPi was 87.0 +/- 10.9 pg/ml, while N-acetyl beta-EPi was 90.8 +/- 7.7 pg/ml (mean +/- SE). When a plasma pool obtained from 3 fetuses in the basal state was extracted and chromatographed on Sephadex G-50, most of the N-acetyl beta-EPi eluted in the same position as the synthetic N-acetyl beta-EP standard. Thus, most of the beta-EPi in the plasma of the unstressed fetus could be accounted for by N-acetylated forms of the peptide. These are the major forms of beta-EP produced by the intermediate lobe of the pituitary. To examine the effects of acute hypoxia on fetal plasma peptide levels, pregnant ewes were exposed to 10% O2 in N2 for 30 min. In 15 studies at 113-142 days gestation, mean fetal PO2 decreased from 21.7 +/- 0.6 to 11.0 +/- 0.7 mm Hg (P less than 0.001). Total beta-EPi increased significantly from 93.0 +/- 17.7 to 527 +/- 146 pg/ml during hypoxia and returned toward basal values after 30 min of recovery to 372 +/- 116 pg/ml (P less than 0.02). Over the same intervals, N-acetyl beta-EPi did not change significantly, with mean levels of 88.5 +/- 10.7, 123 +/- 16.3, and 130 +/- 16.8 pg/ml. This shows that the increase in total beta-EPi with hypoxia could not be accounted for by an increase in N-acetyl beta-EPi. Our finding that most of the total beta-EPi in the circulation of the undisturbed fetus is N-acetyl beta-EPi favors an intermediate lobe origin. Since beta-EP is inactivated by N-acetylation, these data suggest that this immunoactivity has little or no biological activity. Enhanced release of total beta-EPi during hypoxia, which could not be accounted for by acetylated forms, suggests that this type of stress activates the anterior pituitary lobe and results in increased plasma concentrations of the biologically active peptide.

Topics: Acetylation; Animals; beta-Endorphin; Carbon Dioxide; Endorphins; Female; Fetal Blood; Fetal Hypoxia; Gestational Age; Hydrogen-Ion Concentration; Oxygen; Pregnancy; Radioimmunoassay; Sheep

In an attempt to determine whether hypoxic-ischemic encephalopathy in and of itself or its associated pathologic conditions lead to increased concentrations of plasma beta-endorphin (beta-ED), measurements were made in three groups of term infants. Group 1 (control) consisted of 8 infants with a mean gestation of 38.6 +/- (SE) 0.4 weeks, a mean birth weight of 3,420 +/- 150 g, and a mean postnatal age of 1.4 +/- 0.7 days. Group 2 consisted of 10 infants with a mean gestational age, birth weight and postnatal age of 40.1 +/- 0.5 weeks, 3,310 +/- 80 g and 3,9 +/- 1.1 days, and group 3 included 6 infants with a mean gestational age, birth weight and postnatal age of 40.4 +/- 1 weeks, 3,650 +/- 310 g, and 2.8 +/- 1 days, respectively. The group 2 and 3 infants suffered clinical and neurological evidence of hypoxic-ischemic brain injury from perinatal asphyxia; however, the infants in group 2 suffered additional problems such as meconium aspiration, persistent fetal circulation with ongoing hypoxemia as measured by transcutaneous or umbilical arterial oxygen monitoring. The group 3 infants were normoxemic after resuscitation. The mean plasma beta-ED concentrations were 19 +/- (SE) 2.7, 103 +/- 35.7 and 25 +/- 4.5 pg/ml in groups 1, 2 and 3, respectively. A significant elevation of plasma beta-ED concentration was observed in group 2 when compared to groups 1 and 3. The association of increased plasma beta-ED concentration in infants with hypoxic-ischemic encephalopathy associated with ongoing hypoxemia suggests that hypoxemia may act as a strong stimulus for plasma beta-ED release in term infants.

Topics: Asphyxia Neonatorum; beta-Endorphin; Birth Weight; Brain Diseases; Endorphins; Female; Fetal Hypoxia; Gestational Age; Humans; Infant, Newborn; Pregnancy

To investigate the developmental changes in the secretion of vasopressin and the potential role of beta-endorphin as a stimulus to the release of vasopressin, the concentrations of these peptides were measured in fetal, newborn, and adult sheep after episodes of induced hypoxia. The studies confirm that hypoxia is a potent stimulus to the release of both vasopressin and beta-endorphin in the fetal animal. In both the newborn lamb and the ewe, more profound hypoxia is necessary for a similar release. In the fetus, the release of both vasopressin and beta-endorphin after hypoxia increased with gestational maturation. A comparison of control concentrations of both peptides, the discordance of release in the newborn lamb, and the absence of a change in concentrations of vasopressin with infusion of beta-endorphin implies that these hormones are released in parallel but independently during hypoxic stress.

Topics: Aging; Animals; beta-Endorphin; Endorphins; Female; Fetal Hypoxia; Fetus; Hypoxia; Oxygen; Pregnancy; Radioimmunoassay; Sheep; Vasopressins

Antisera suitable for human beta-endorphin and beta-lipotropin radioimmunoassay were developed, and radioimmunoassays were established to measure these peptides in umbilical cord plasma, with silicic acid extraction and gel chromatography used to separate the beta-endorphin from the beta-lipotropin fraction. These two peptides were determined in umbilical venous plasma from 64 newborn infants. Umbilical vein beta-endorphin and beta-lipotropin concentrations averaged 38.5 +/- 3.2 and 50.4 +/- 4.1 (+/- SE) fmoles/ml in the 54 newborn infants without and 115 +/- 18 and 110 +/- 25 fmoles/ml in the 10 newborn infants with apparent fetal distress. Neither the presence or absence of labor nor the route or mode of delivery was found to affect umbilical vein beta-endorphin or beta-lipotropin concentrations. However, cord plasma levels of both peptides were significantly elevated in conjunction with fetal distress, as evidenced by prolonged bradycardia, late and prolonged variable fetal heart rate decelerations, or fetal acidosis. In 18 of 22 pairs of simultaneously measured umbilical venous and arterial beta-endorphin and beta-lipotropin concentrations in newborn infants without apparent intrapartum distress, the venous beta-endorphin concentrations, which averaged 40.4 +/- 3.5 fmoles/ml, were significantly higher than the arterial beta-endorphin levels, with a mean of 28.5 +/- 4.2 fmoles/ml. No significant umbilical arteriovenous concentration difference could be observed for beta-lipotropin. This suggests that at least a portion of the coad plasma beta-endorphin is derived from the placenta. The ratio of umbilical arterial to venous beta-endorphin concentrations rose as the absolute cord plasma beta-endorphin levels increased. Furthermore, both the molar umbilical venous and arterial beta-lipotropin to beta-endorphin ratios decreased significantly in association with intrapartum fetal distress. These data indicate tat the stress-related increase in umbilical plasma beta-endorphin exceeds that of beta-lipotropin and may be, at least in part, of fetal origin. Umbilical venous beta-endorphin and beta-lipotropin levels of neonates whose mothers did not receive meperidine or other narcotics agents did not differ from those of neonates whose mothers were given meperidine or other narcotics during labor. Our data, in conjunction with those of others, are consistent with the hypothesis that fetal hypoxia causes the release of neurotransmitters such as beta-endorphin, wh

Topics: beta-Endorphin; beta-Lipotropin; Chromatography, Gel; Delivery, Obstetric; Endorphins; Female; Fetal Blood; Fetal Hypoxia; Labor, Obstetric; Pregnancy; Radioimmunoassay; Silicic Acid