Investigation of the oxytocin receptor at the molecular level.

Before the onset of labor, the myometrium becomes extremely sensitive to oxytocin, for which it is a primary target tissue, because of a tremendous increase in the number of oxytocin receptors. To study this dynamic expression and regulation of the receptor, we cloned the human oxytocin receptor cDNA in 1992 and characterized its expression in female reproductive organs and in the rat brain using the receptor cDNA and anti-oxytocin receptor monoclonal antibodies. In the uterus, we revealed that oxytocin receptor expression is mainly regulated at the transcriptional level. For the investigation of this transcriptional regulation, we isolated and characterized the human oxytocin receptor gene. The gene contains 3 introns and 4 exons and is assigned to 3p26.2 of human chromosome 3. In the 5'-upstream region of this gene, we found several known binding sites for transcription regulation factors including the nucleofactor-interleukin 6 binding consensus sequence and an acute phase reactant-responsive element. Our findings on the structure of the oxytocin receptor gene should help to elucidate the mechanism by which expression of the gene is induced dramatically at parturition in the uterus and how the gene is regulated in other organs such as the mammary gland and central nervous system.