Effects of Naloxone on the Preparturient Increase in Adrenocorticotrophin and Cortisol in Foetal Sheep

Abstract

Abstract Parturition in sheep is preceded by a rapid increase in foetal pituitary-adrenal activity. Administration of exogenous opioids increases foetal plasma adrenocorticotrophin (ACTH) and cortisol concentrations after Day 125 of pregnancy (term = 145 days). In order to test the hypothesis that endogenous opioids regulate the increase in pituitary-adrenal activity prior to parturition in foetal sheep, we measured changes in plasma ACTH and cortisol in response to administration of either naloxone (1.2 mg intravenous bolus followed by a 2.5 mg/h continuous infusion for 2 h; foetal body weight approximately 2.5 kg) or saline to chronically catheterized foetal sheep at 2-day intervals between Day 140 and the onset of parturition. In addition, we utilized a computerized algorithm (Munro) to examine the precise characteristics of ACTH and cortisol secretion in control and naloxone-treated foetuses. The pattern of ACTH and cortisol secretion in saline-infused control foetuses was highly pulsatile but varied considerably between individual foetuses. ACTH pulses occurred on average every 40 min but were not always coincident with pulses of cortisol. There were no significant changes in average ACTH concentrations, pulse frequency or amplitude between foetuses sampled at 3 to 4 and 1 to 2 days before parturition. In contrast, average cortisol concentrations and pulse amplitude were significantly (P < 0.05) increased, whereas pulse frequency was reduced, in foetuses at 1 to 2 days before parturition. Naloxone caused a significant (P < 0.05) inhibition of ACTH concentrations when compared with pretreatment values and with saline-treated controls, an effect which persisted for at least 2 h after the end of naloxone infusion. However, there were no significant differences during naloxone treatment in the frequency or amplitude of ACTH or cortisol pulses nor in the mean cortisol concentration. We conclude that ACTH and cortisol are secreted in a pulsatile fashion in the late gestation foetal sheep and that these pulses are not always coincident with each other. Blockade of endogenous opioid activity during the preparturient increase in pituitary-adrenal activity in foetal sheep, results in a reduction in plasma concentrations of ACTH. These results therefore provide evidence for the tonic regulation of foetal pituitary-adrenal activity by endogenous opioids during the final days prior to birth in the sheep.