CONTINUOUS INTRAFETAL INFUSION OF PROSTAGLANDIN E(2) PREMATURELY ACTIVATES THE HYPOTHALAMO-PITUITARY-ADRENAL AXIS AND INDUCES PARTURITION IN SHEEP

This study has investigated the effect of continuous intrafetal infusi on of PGE(2) or saline on hormone concentrations: and the length of ge station in sheep. Fetal and maternal vascular catheters were surgicall y implanted at 112.3 +/- 1.3 days (n = 10), and the infusions were sta rted at 121 +/- 1.2 days of gestation (term = 147). Fetuses vi ere inf used with either PGE(2) (n = 5; 2 (mu g/min for 48 h and then increase d. to 4 mu g/min for the remainder of the experiment) or the vehicle s olution (n = 5; sterile isotonic saline) via the fetal carotid artery. In the PGE(2)-infused group, fetal and maternal plasma PGE(2) concent rations increased (P < 0.001) after the change to the higher dose 1 at e (4 mu g/min) and remained elevated, fetal plasma immunoreactive ACTH (ir-ACTH) concentrations dramatically increased after the start of th e infusion being maximal at 11 h before decreasing to match concentrat ions exhibited by the saline-infused group. Fetal plasma cortisol conc entrations increased after the start of the PGE(2) infusion (P = 0.05) and increased further after the change to the higher dose rate of 4 m u g/min (P < 0.001. Concentrations of PGE(2), ir-ACTH, and cortisol in the saline-infused group did not change until labor. Plasma concentra tions of PGE(2) (P < 0.001) and ir-ACTH (P < 0.005) increased on tile day of labor in both treatment groups, and feral cortisol concentratio ns increased (P < 0.001) in both groups in the last few days before la bor. The proportion or low molecular weight ir-ACTH in the plasma of P GE(2)-infused fetuses was significantly higher than that uf saline-inf used fetuses (P < 0.001) during the first 15 days of infusion. In the saline-infused group, the proportion of low molecular weight ir-ACTH i ncreased in the last few days before labour (P = 0.001), whereas no ch ange was seen in PGE(2)-infused fetuses at this time. Maternal plasma progesterone concentrations decreased in both groups in the last few d ays before labor (P < 0.001). Fetuses infused with PGE(2) delivered at 138.4 +/- 2.1 days, whereas control fetuses infused with saline deliv ered at 148.2 +/- 0.5 days (P < 0.01). The spontaneous increase in PGE (2) preceding normal labor may thus play an important role in activati on and maturation of the hypothalamic-pituitary-adrenal asia in fetal sheep.