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.