MORPHINE STIMULATES ADRENOCORTICOTROPIN AND CORTISOL RELEASE IN THE LATE-TERM OVINE FETUS

Opiates are widely used as obstetrical analgesics during pregnancy and , as such, their interactions with the fetal endocrine system may have important consequences. In this study, the effects of morphine admini stration to fetal sheep in utero on fetal plasma immunoreactive (ir)-A CTH and ir-cortisol were examined. At the lowest dose administered (0. 6 mg/h, i.v.) morphine reduced, although not significantly, plasma ir- cortisol levels. A dose-dependent stimulation of cortisol release was observed with higher doses of morphine. Doses of 2.5 and 5.0 mg/h morp hine resulted in a significant increase in ir-cortisol with a change f rom control levels equal to 9.6 +/- 1.1 ng/mL (p = 0.03) and 17.6 +/- 5.1 ng/mL (p = 0.03), respectively. This increase in plasma ir-cortiso l was associated with a significant increase in ir-ACTH (111.8 +/- 23. 2 pg/mL versus 42.8 +/- 5.1 pg/mL; p = 0.02) that was naloxone-reversi ble. These effects of morphine were observed in fetal lambs only >125 d of gestation, suggesting a maturation of functional opioid receptors in the ovine fetal hypothalamic-pituitary-adrenal axis after this tim e.