Dose-related effect of IGF-I on placental prostanoid release.
Prostanoids play an important role throughout all of pregnancy and during the initiation and progress of labor. The human placenta at term produces large quantities of prostanoids, yet little is known of the factors regulating their biosynthesis. In a previous study we observed that insulin-like growth factor I (IGF-I) specifically inhibits thromboxane B2 (TxB2) and prostaglandin F2 alpha (PGF2 alpha) from human term placental explants. In these studies we have defined the dose-related action of IGF-I on the release of placental prostanoids. With use of a perifusion system, the basal release of prostaglandin E2 (PGE2), PGF2 alpha, TxB2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) from human term placental explants increased from the fifth hour in culture, while the release of 13,14-dihydro-15-keto-PGF2 alpha (PGFM) remained constant. The addition of IGF-I (5.2-83.3 ng/mL) to the perifusing medium effected an inhibition of TxB2 and PGF2 alpha. The release of TxB2 was inhibited in a dose-related fashion from the initiation of IGF-I treatment and throughout the five hours of treatment, whereas the inhibition of PGF2 alpha was significant only at a dose of 83.3 ng/mL of IGF-I. Yet, the release of 6-keto-PGF1 alpha, PGE2, or PGFM was not altered by any dose of IGF-I studied. Because both TxB2 and PGF2 alpha are vasoconstrictors, we have proposed that IGF-I may enhance vasodilation in the placenta. Therefore, IGF-I may allow for increased blood flow, thus affecting the maintenance of pregnancy and the supply of nutrients available for the growth of the fetus.
Siler-Khodr
T M
TM
Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, USA.
Forman
J
J
Sorem
K A
KA
D015237:Dinoprost / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000493:pharmacokinetics; D015232:Dinoprostone / Q000378:metabolism / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development / Q000187:drug effects; D011464:Epoprostenol / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000494:pharmacology*; D010477:Perfusion; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism / Q000493:pharmacokinetics*; D013928:Thromboxane A2 / Q000378:metabolism / Q000493:pharmacokinetics; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000493:pharmacokinetics; D013997:Time Factors
D011453:Prostaglandins; D013929:Thromboxane B2; D013928:Thromboxane A2; D007334:Insulin-Like Growth Factor I; D015237:Dinoprost; D011464:Epoprostenol; D015232:Dinoprostone