Katariina Salminen

Corticotropin-releasing hormone in amniotic fluid during gestation and labor and in relation to fetal lung maturation

Corticotropin-releasing hormone was discovered in the placenta, and its concentration in the maternal plasma was found to increase greatly during the latter half of pregnancy. We studied the concentration of immunoreactive corticotropin-releasing hormone in amniotic fluid in 59 uncomplicated and in 73 complicated pregnancies. The mean (+/- SE) value of corticotropin-releasing hormone in amniotic fluid in uncomplicated pregnancies was significantly higher in the third (24.1 +/- 3.3 pmol/L) than in the second (9.1 +/- 0.7 pmol/L) trimester, but no change was found during labor. In groups matched by gestational age, larger mean values of corticotropin-releasing hormone and cortisol were observed in the group in which the lecithin/sphingomyelin ratio was greater than 2 or the phosphatidylglycerol test was positive than in the group with a lecithin/sphingomyelin ratio less than 2 or a negative phosphatidylglycerol test result. In samples taken at an interval of 1 to 3 weeks, concomitant increases in corticotropin-releasing hormone and cortisol levels were found with the appearance of phosphatidylglycerol. Concentrations of corticotropin-releasing hormone in amniotic fluid were elevated in patients with diabetes and in women with preeclampsia and intrauterine growth retardation. We conclude that the intrauterine release of corticotropin-releasing hormone increases during the last trimester. This may stimulate the fetal pituitary-adrenal axis and promote fetal maturation.

Immunoreactive corticotropin-releasing factor and corticotropin during pregnancy, labor and puerperium

Concentrations of immunoreactive corticotropin releasing factor (CRF) and corticotropin (ACTH) in the plasma were studied in healthy pregnant women. Concentration of CRF was near the detection limit of the assay (2.5 pmol/l) until the 16th week of pregnancy, increasing thereafter significantly towards term: the mean values (+/- S.E.) at weeks 8-11, 12-15, 16-19, 20-23, 24-27, 28-31, 32-35, and 36-40 were 2.9 +/- 0.42, 2.9 +/- 0.72, 5.2 +/- 1.1, 10.2 +/- 5.8, 14.6 +/- 2.0, 32.8 +/- 4.8, 63.6 +/- 9.2, and 187 +/- 39 pmol/l, respectively. The mean concentration of CRF did not increase during labor, and it decreased rapidly after delivery. On the contrary, the mean plasma level of ACTH increased only slightly during late pregnancy, but during labor the increase was significant. These findings suggest that CRF in maternal circulation is not primarily involved in the regulation of maternal ACTH secretion, and the stress of labor does not increase the release of CRF, which probably originates mainly from the placenta.

Immunoreactive β-endorphin is demonstrable in the secretory but not in the proliferative endometrium

The presence of immunoreactive beta-endorphin (ir beta-E) in the endometrium was studied by immunoperoxidase staining of tissue sections at various stages of the menstrual cycle. Ir beta-E was found in the endometrium during the secretory phase of the cycle, from the fourth postovulatory day to the desquamating phase, but not in the proliferative phase or during the first three postovulatory days of the cycle. Ir beta-E was located in the cytoplasm of the epithelial cells of the glands. Samples of endometrium were homogenized, and peptides were extracted with Sep Pak C18 cartridge, followed by purification of ir beta-E by cation-exchange high-pressure liquid chromatography. In samples of secretory endometrium, a peak of ir beta-E was found with identical location of that of reference beta-E. The concentration of ir beta-E in the secretory endometrium varied from 5.0 to 12.6 pg/g of tissue. The appearance of ir beta-E in the endometrium during the secretory phase may have importance in the early events of reproduction.

Response of plasma endorphins to running exercises in male and female endurance athletes.

We studied the responses of plasma concentrations of beta-endorphin, beta-lipotropin, and corticotropin to an exhaustive graded treadmill exercise, to an anaerobic treadmill exercise, and to a sub-maximal outdoor running exercise in 5 male and in 5 female endurance athletes. During the graded treadmill exercise, the mean plasma level (+/- SE) of beta-endorphin in men rose from 1.2 +/- 0.1 to 8.1 +/- 0.7 pmol.l-1, beta-lipotropin rose from 1.6 +/- 0.5 to 7.4 +/- 1.4 pmol.l-1, and corticotropin rose from 4.9 +/- 1.0 to 31 +/- 3.3 pmol.l-1. In women, the mean level of beta-endorphin rose from 1.2 +/- 0.2 to 8.2 +/- 1.8 pmol.l-1, beta-lipotropin rose from 1.4 +/- 0.1 to 8.1 +/- 2.0 pmol.l-1, and corticotropin rose from 3.3 +/- 0.4 to 28 +/- 7.9 pmol.l-1. Concentrations of endorphins and corticotropin increased significantly also during the anaerobic exercise test. In response to sub-maximal running exercise, no significant change was found. These results showed a relationship between the intensity of exercise and the secretion of pro-opiomelanocortin-related peptides, and there were no differences between the groups of trained men and women.

Plasma β‐endorphin immunoreactivity in premenstrual tension

Summary. Plasma samples were collected twice during the follicular phase and three times during the luteal phase of the menstrual cycle in 12 women with premenstrual tension (PMT) and in 14 control subjects without symptoms. Concentrations of β‐endorphin (β‐E) immunoreactivity, cortisol, oestradiol, progesterone and LH were determined. Comparison of the mean concentrations of LH, cortisol, oestradiol and progesterone did not reveal any statistically significant differences between the PMT and the control groups. In the early luteal phase, the mean plasma β‐E immunoreactivity was lower in the PMT group (10.7, SE 0.7 pg/ml) than in the control group (14.6, SE 1.6 pg/ml, P<0.05), suggesting that endorphin secretion is decreased in PMT. No significant change in the plasma β‐E level was found in the PMT patients between the follicular and luteal phase when symptoms appeared. This does not exclude the possibility that in the central nervous system abnormal changes occur in the activity of endogenous opioids in PMT.

Plasma corticotropin-releasing hormone, corticotropin, and endorphins at rest and during exercise in eumenorrheic and amenorrheic athletes *

The hypothalamic-pituitary response to exercise was studied in 12 amenorrheic and in 9 eumenorrheic athletes by comparing the concentrations of corticotropin-releasing hormone (CRH), corticotropin (ACTH), and endorphins (beta-endorphin + beta-lipotropin) in plasma at rest and during an acute exercise on a bicycle ergometer requiring 80% and 100% of the maximal oxygen uptake (VO2 max). Plasma CRH levels did not change during the exercise, and the mean CRH values did not differ between the amenorrheic and eumenorrheic groups. In both groups, significant increases in the response to exercise were found in the concentrations of ACTH and endorphins. The only significant difference between the groups was a larger mean pre-exercise concentration of endorphins in amenorrheic than in eumenorrheic athletes (4.8 +/- 0.8 standard error [SE] and 2.9 +/- 0.2 pmol/l, respectively). It is concluded that in amenorrheic athletes the capacity of the anterior pituitary to secrete ACTH and endorphins in response to exercise does not significantly differ from that in eumenorrheic athletes, although basal endorphin secretion may be increased.

Plasma |[beta]|-Endorphin in Perinatal Asphyxia and Respiratory Difficulties in Newborn Infants

ABSTRACT. The effects of intrauterine stress and birth asphyxia on the plasma concentration of β-endorphin (β- E) in cord blood and in venous blood at the age of 2 h was investigated in newborn infants. Term infants with acute birth asphyxia (n=11), infants born to mothers with preeclampsia (n=15), and prematures with respiratory difficulties (n=4) were entered into the study. Twenty control infants were studied; 12 were born after spontaneous delivery and eight after elective cesarean section. After normal spontaneous delivery, the plasma β-E level decreased significantly, the median values being 17 pmol/ liter at birth and 9.3 pmol/liter at the age of 2 h, whereas after elective cesarean section it remained unchanged (13 and 13 pmol/liter, respectively). In acute asphyxia the plasma β-E level varied widely at birth, from 9.7 to 108 pmol/liter. At the age of 2 h, the β-E level was high (26 to 83 pmol/liter) in those asphyctic infants who required prolonged mechanical ventilation, but it fell to the range of 1.6-13 pmol/liter when the infant recovered rapidly. The β-E level was not increased in the preeclampsia group, not even in small for gestational age infants. In preterm newborn infants with respiratory difficulties, a significant postnatal rise of plasma β-E level was found, the β-E value varying from 7.3 to 16 pmol/liter at birth and from 61 to 168 pmol/liter at the age of 2 h. These results indicate that increased β-E secretion is associated with respiratory difficulties in the newborn infant.

Localization and ceoncentration of β- and β-lipotrophin in human placenta

Abstract Immunohistochemical staining of placental tissue for β-endorphin immunoreactivity was positive in the syncytiotrophoblast in both early and term pregnancy. Cation-exchange liquid chromatography and radioimmunoassay revealed peaks of β-endorphin and β-lipotrophin and a third immunoreactive peak of unknown nature. The concentration of β-endorphin was higher in the placental tissue than it was in the maternal or cord plasma. β-Lipotrophin was not detected in all placentae studied. We did not find any effect of gestational age on tissue concentrations of endorphins in the placenta, nor was there any significant difference in the placental endorphin content between placentae collected at elective caesarean section before labour and after spontaneous vaginal delivery.

Plasma endogenous opioids and dexamethasone suppression test in depression

Plasma levels of beta-endorphin plus beta-lipotropin were determined in 35 hospital patients with depression and in 23 controls before and after administration of 1 mg of dexamethasone (dxm). Dxm suppressed opioid secretion in both groups. The opioid levels of the patients were significantly higher than those of the controls both before and after dxm. All the controls were cortisol suppressors. Among the patients the post-dxm opioid levels of cortisol nonsuppressors (n = 14) were higher than those of cortisol suppressors (n = 21). A significant correlation between the opioid and cortisol levels was found in the patients. There was a significant association between the use of neuroleptics and high opioid levels, but the difference between the patients and the controls was not explained by the effect of any single class of drugs. The results support the concept of hypersecretion of corticotropin-releasing factor in depression.

Rapid extraction and separation of plasma β-endorphin by cation-exchange high-performance liquid chromatography

Cation-exchange high-performance liquid chromatography (HPLC) was used to increase the sensitivity and specificity of the radioimmunoassay of plasma beta-endorphin. Proteins were precipitated from a 0.5 to 2.5 ml sample of plasma with 60% acetonitrile at pH 4.7. The supernatant was subjected to cation-exchange HPLC. Gradient elution with volatile buffers was used to separate beta-endorphin from beta-lipotropin. The beta-endorphin fraction (1.8 ml) was concentrated by lyophilization and subjected to radioimmunoassay. In healthy pregnant women at labour plasma concentration of beta-endorphin varied from 105 to 403 pg/ml. In healthy non-pregnant women plasma concentration of beta-endorphin was low, exceeding the detection limit (4 pg/ml) of the assay in only one of the 7 subjects studied.