Ontogeny of immunoreactive prostaglandin endoperoxide synthase isoforms inovine fetal pituitary, hypothalamus and brainstem

Parturition is initiated in sheep by an increase in the activity of the fet al hypothalamus-pituitary-adrenal (HPA) axis. Prostaglandins, known to augm ent the activity of this endocrine axis, have long been proposed as involve d in the initiation of paturition. We have previously demonstrated that end ogenously produced prostanoids augment the activity of the HPA axis, and we have proposed that the increased production of prostanoids within the feta l brain or pituitary at the end of gestation might be involved in the initi ation of parturition. An important regulatory step in the biosynthesis of p rostanoids is the activity of prostaglandin endoperoxide synthase (PGHS). T he 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 p ituitary at the end of gestation. We used immunoblot analysis to measure th e abundance of immunoreactive PGHS-1 and PGHS-2 in pituitary, hypothalamus and brainstem collected from fetuses of known gestational ages, We found th at the abundance of PGHS-1 was weakly but significantly increased at the en d of gestation in the pituitary and brainstem, The abundance of PGHS-2, on the other hand, increased exponentially in the pituitary and hypothalamus w ith highest concentrations found in term fetuses, We conclude that these en zymes are developmentally regulated in pituitary and in brain regions impor tant for HPA axis control. We speculate that the increased enzyme's abundan ce results in increased prostanoid biosynthesis near term, and is a link in the chain of events which initiates parturition, Copyright (C) 2000 S. Kar ger AG, Basel.