The trigger for parturition in sheep: fetal hypothalamus or placenta?

The fetal pituitary-adrenal axis plays a pivotal role in the mechanisms leading to parturition in sheep. Fetal cortisol concentrations gradually increase in the last 15 days before term, with a marked increase occurring in the last 3-4 days. Some mechanism causes a marked increase in the stimulatory drive to the fetal pituitary resulting in increased secretion of ACTH from the pituitary, and subsequent cortisol secretion from the adrenal gland. In this paper we discuss the roles of the hypothalamus and placenta in triggering the onset of labour in sheep. We have shown that prostaglandin E2 can stimulate the release of ACTH and cortisol in the intact fetus and we believe that this could be mediated by the release of CRH and AVP. Although CRH and AVP are present in the fetal hypothalamus and are capable of being released, these factors may not be released until approximately 135 days of gestation. One fundamental question in relation to parturition remains unanswered: how are the high concentrations of cortisol in fetal plasma sustained given that cortisol has an inhibitory feedback effect on the release of CRH and ACTH secretion? We discuss the possibility that the placenta provides an additional trophic drive to both the pituitary and adrenal glands which contributes towards the sustained elevated cortisol concentrations needed to initiate parturition. The placenta may initiate the hypothalamus and PGE2 and/or CRH, secreted by the placenta, may stimulate pituitary ACTH release.