Ontogeny of immunoreactive prostaglandin endoperoxide synthase isoforms in ovine fetal pituitary, hypothalamus and...

Parturition is initiated in sheep by an increase in the activity of the fetal hypothalamus-pituitary-adrenal (HPA) axis. Prostaglandins, known to augment the activity of this endocrine axis, have long been proposed as involved in the initiation of paturition. We have previously demonstrated that endogenously produced prostanoids augment the activity of the HPA axis, and we have proposed that the increased production of prostanoids within the fetal brain or pituitary at the end of gestation might be involved in the initiation of parturition. An important regulatory step in the biosynthesis of prostanoids is the activity of prostaglandin endoperoxide synthase (PGHS). The present study was designed to test the hypothesis that the abundance of one or both isoforms of PGHS (PGHS-1 and PGHS-2) increase in brain and/or pituitary at the end of gestation. We used immunoblot analysis to measure the abundance of immunoreactive PGHS-1 and PGHS-2 in pituitary, hypothalamus and brainstem collected from fetuses of known gestational ages. We found that the abundance of PGHS-1 was weakly but significantly increased at the end of gestation in the pituitary and brainstem. The abundance of PGHS-2, on the other hand, increased exponentially in the pituitary and hypothalamus with highest concentrations found in term fetuses. We conclude that these enzymes are developmentally regulated in pituitary and in brain regions important for HPA axis control. We speculate that the increased enzyme's abundance results in increased prostanoid biosynthesis near term, and is a link in the chain of events which initiates parturition.