The molecular basis of oxytocin and oxytocin receptor gene expression in reproductive tissues.

Abstract

Transcriptional regulation of the oxytocin and oxytocin receptor genes underly to a large degree the highly specific and often transient physiologies associated with this peptide hormone system. Using a variety of homologous transcription assays we have endeavoured to identify and characterize the cis and trans elements responsible for the regulation in vivo of the oxytocin peptide gene and the gene for the oxytocin receptor. The bovine ovarian granulosa cell model is a primary culture system where under stimulation by insulin or IGF-I and LH the endogenous oxytocin gene is massively upregulated. We have identified a proximal response element at -160, which in vivo binds the competing nuclear receptors, SF1 and COUP-TF. Additionally ovarian specific transcription factors bind at two additional sites in the distal promoter region. For the bovine oxytocin receptor gene, we have taken advantage of the high endogenous expression of the receptor in the endometrium of the estrous cycle. Using a combination of primary cell culture techniques and in vitro binding of nuclear protein extracts from tissues expressing the receptor in vivo, we have shown there to be a combination of constitutive and inhibitory elements controlling oxytocin receptor gene expression. Similar results were obtained for the human oxytocin receptor gene. At birth there may additionally be a specific stimulatory effect on transcription in the myometrium.