Regulation of oxytocin receptor gene expression in sheep: tissue specificity, multiple transcripts and mRNA editing

The increase in uterine oxytocin receptor concentrations over the late lute al phase of the oestrous cycle in sheep is thought to play an important rol e in the regulation of the duration of the cycle by facilitating the effect of oxytocin on uterine prostaglandin release. Experiments indicated that o xytocin receptor mRNA expression in the endometrium was high at oestrus com pared with at days 2, 7 and 12 of the oestrous cycle. The amount of oxytoci n receptor mRNA expression in the pituitary gland did not show any signific ant differences during the oestrous cycle. Oxytocin receptor cDNA was obtai ned and characterized from ovine uterine endometrium on day 15 of the oestr ous cycle, using RT-PCR techniques, to study the mechanisms underlying the resolution of oxytocin receptor expression. The cDNA sequence for the oxyto cin receptor gene in sheep was found to be similar to that described previo usly, except for a difference of seven nucleotides. These nucleotide differ ences resulted in changes in four of the deduced amino acids in the oxytoci n receptor sequence. The heterogeneity of the different sized oxytocin rece ptor transcripts in sheep is due, at least in part, to the alternative use of polyadenylation sites. Northern hybridization confirmed that the oxytoci n receptor gene is expressed in ovine corpus luteum. The investigations on oxytocin receptor gene expression indicate that the patten of oxytocin rece ptor gene expression in sheep is not only tissue-specific, but also highly function-related. Evidence was obtained of mRNA editing in both the coding and the 3'-untranslated (3'UTR) regions of oxytocin receptor gene transcrip ts in ovine endometrium; this was the first demonstration of this phenomeno n for oxytocin receptor mRNA. The present results indicate that the observe d differences in oxytocin receptor mRNA sequences for the different oxytoci n receptor populations in endometrium are due to mRNA editing. mRNA editing of oxytocin receptor transcripts may be reflected in changes in the amino acid composition of the carboxyl terminus of the receptor, which would expl ain the differences in the observed responses to an oxytocin challenge.