Effect of IGF-I on placental thromboxane and prostacyclin release in severe intrauterine growth retardation.
Our recent findings that IGF-I inhibits placental thromboxane (TxB2) release (1, 2) and that prostanoid release from placentas or certain pregnancies complicated by intrauterine growth retardation (IUGR) is decreased [Sorem KA, Siler-Khodr TM, Placenta, 16:503-515, 1995] led us to investigate the effect of IGF-I on prostanoid release from placentas of IUGR pregnancies. The placental response of 6-keto-prostaglandin F1a (6-keto-PGF1a) and thromboxane (TxB2) to IGF-I in severe IUGR (n = 5) was compared with the response in normal pregnancies (n = 6). Placentas were perifused with medium containing IGF-I at doses of 0, 5.2, 10.4, 20.8, and 83.3 ng/ml. In three of the five IUGR placentas (responsive group), incubation with IGF-I resulted in an inhibition of TxB2, attaining significantly greater inhibition at a lower dose of IGF-I than the normal placental response. However, in two of the five IUGR placentas (non-responsive group), the TxB2 was insensitive to the normal inhibitory action of IGF-I. The baseline production of prostanoids from the IUGR placentas was not predictive of their response to IGF-I. Moreover, 6-keto-PGF1a was not inhibited in any of the placentas, IUGRs, or normals. However, the ratio for TxB2 over 6-keto-PGF1a basal production rate from the zero treatment time to the fifth hour was significantly less in the nonresponsive IUGR placentas than for the responsive IUGR placentas or for the normal placentas. Certain IUGR placentas demonstrated a significant suppression of TxB2 with IGF-I, whereas other IUGR placentas were insensitive to exogenous IGF-I. A decreased and unchanging ratio of TxB2/6-keto-PGF1a production rate was characteristic of the nonresponders.
Sorem
K A
KA
Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, USA.
Siler-Khodr
T M
TM
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis / Q000378:metabolism*; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D013929:Thromboxane B2 / Q000032:analysis / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000032:analysis; D014665:Vasodilator Agents / Q000032:analysis
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D007334:Insulin-Like Growth Factor I