Evidence for 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene C4(LTC4) in the onset of labor.
Arachidonic acid is metabolized by cyclooxygenase leading to prostaglandins (PG), and by lipoxygenases leading to hydroxyeicosatetraenoic acids (HETE) and leukotrienes (LT). PGs are potent uterine constrictors. 5-HETE and LTC4 also stimulate uterine contractions, but their role in labor is not known. To estimate the activities of these pathways before parturition and their relationship to uterine contractility, amniotic fluid (AF) concentrations of 5-HETE, LTC4 and PGF2 alpha were determined in 5 chronically catheterized rhesus monkeys. Uterine contractility was continually assessed by changes in AF pressure.


RESULTS
AF concentrations at the time of intrauterine surgery were 4.4 +/- 0.8 ng/ml for 5-HETE and 2.5 +/- 0.7 ng/ml for LTC4. PGF2 alpha levels were nondetectable. Indomethacin infusion into the mother, although effective in suppressing PGF2 alpha levels, did not prevent the onset of premature labor and vaginal delivery in 2 animals. PGF2 alpha did not increase in 1 monkey with term labor. Approximately 1 week before delivery, 5-HETE and LTC4 concentrations increased sharply in all animals in association with a nocturnal pattern of labor contractions. Peak AF concentrations during labor were 5-HETE: 40 +/- 8 ng/ml, LTC4: 20 +/- 4 ng/ml, and PGF2 alpha: 5.4 +/- 2.1 ng/ml.


CONCLUSIONS
LTC4 and 5-HETE stimulate uterine contractility in vitro, and probably act in concert with PGF and PGE to stimulate uterine contractions during parturition. HETEs may also act as a signal to recruit white blood cells to the uterus and to activate them, there to augment PG and LT production and act as a first line of defense against any infection that might enter the uterus from the vagina during or after delivery.


CONCLUSIONS
1) 5-HETE and LTC4, but not PGF2 alpha, are associated with uterine contractility after preterm intrauterine surgery. Surprisingly, AF PGF2 alpha levels were nondetectable for 1 to 2 weeks after surgery. 2) 5-HETE and LTC4 are present in higher concentrations than PGF2 alpha in AF. 3) 5-HETE, LTC4 and PGF2 alpha all increase with the onset of labor. AF concentrations of 5-HETE and LTC4 are significantly higher than PGF2 alpha before and during term and preterm labor. 4) Labor can occur with suppressed PGF2 alpha levels, but with increasing 5-HETE and LTC4 levels. 5) These data suggest that 5-HETE and LTC4 are important components of the parturitional process, and they challenge the dogma that PGs are the universal mediators of labor.
Walsh
S W
SW
Department of Obstetrics and Gynecology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0034.
D000653:Amniotic Fluid / Q000737:chemistry / Q000502:physiology; D000818:Animals; D015237:Dinoprost / Q000032:analysis / Q000502:physiology; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis / Q000502:physiology*; D007743:Labor, Obstetric / Q000502:physiology*; D008253:Macaca mulatta; D011247:Pregnancy; D013189:SRS-A / Q000032:analysis / Q000502:physiology*
D006893:Hydroxyeicosatetraenoic Acids; D013189:SRS-A; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D015237:Dinoprost