Effect of late hypothalamo-pituitary disconnection on the development of the HPA axis in the ovine fetus and the initiation of parturition

The studies of Liggins et al. in which fetuses stalk-sectioned from day 116 onwards delivered at or near term, suggested that a connection between the fetal hypothalamus and pituitary is not essential for parturition to occur. The objective of this study was to repeat these experiments on the effects of pituitary stalk sections at different gestational ages and include information on the plasma concentrations of key fetal hormones. We have used the more sophisticated technique of hypothalamo-pituitary disconnection (HPD) at either of two gestational age ranges (123-127 days or 133-135 days). Completeness of the procedure was assessed by demonstrating an attenuated prolactin response to chlorpromazine challenge. Following HPD, gestation was prolonged for at least eight days beyond term (146.2 ± 1.5 days) in 9 of the 10 fetuses operated. Fetal plasma ACTH1-39 concentrations were not different between the HPD and control fetuses, increasing in all groups with increasing gestation. Fetal plasma cortisol concentrations increased (P <0.01) in control fetuses over gestation. Cortisol concentrations did not change significantly in the day 125 HPD group following HPD but increased in the day 135 HPD group (P <0.05) with advancing gestation. These latter concentrations, however were markedly less (P <0.001) than those for control fetuses prior to parturition. Fetal and maternal plasma PGE2 concentrations increased (P <0.01) in the control group over gestation but did not change following HPD. Maternal plasma progesterone concentrations decreased (P <0.05) after day 143 in the control group but did not change in the HPD group. There was no change in maternal plasma concentrations of prostaglandin FM in the HPD group. These findings demonstrate that hypothalamic connection to the pituitary needs to be maintained until at least day 135 of gestation for the initiation of parturition at term.