Effect of day of pregnancy and pregnancy terminating agents on prostaglandin synthesis and metabolism and histamine metabolism in the rat utero-placental fetal complex and lung

Abstract

Synthesis and metabolism of prostaglandins (PG) in the rat placenta during the first two-thirds of pregnancy is low with the exception of a large peak of activity on day 11. During the last third of pregnancy placenta PG-synthesis is low but PG-metabolism increases sharply. In contrast, uterine PG synthesis is low during the first two-thirds of gestation but increases during the remainder of pregnancy, peaking at parturition. Uterine PG-metabolism is low throughout pregnancy. Fluctuation in sex steroid levels during pregnancy may be related to changes in PG-synthesis and metabolism. Maintenance of vital functions in pregnancy may require timed changes in prostaglandin as well as hormonal balance. The non-hormonal non-prostaglandin compounds L-10503 (2-(3-methoxyphenyl)-5,6-dihydro -s-triazole [5,1-a]-isoquinoline) and L-11204 (2-(3-ethoxyphenyl)-5,6-dihydro-s-triazole [5,1-a]-isoquinoline) which terminate pregnancy after blastocyst implantation in the uterus, inhibits PG-metabolism. Administration of these compounds to rats on day 9 of gestation reduces PG-metabolism in the placenta, uterus and lungs whereas treatment on pregnancy days 13 or 15 decreases PG-metabolism only in the maternal and fetal lungs. PG-synthesis is not affected under these conditions. Male and non-pregnant female rats treated with L-10503 and 24 h later given [ 3H]-PGF 2α. or [ 3H]-PGE 1, have a reduced ability to metabolize PG as measured in plasma. L-11204 administered on day 9 of pregnancy increased placental, uterine and fetal histamine. Placental histaminase was also increased by this treatment. Alteration of PG and/or histamine metabolism may be involved in the anti-fertility activity of these novel compounds.