The structure and regulation of the oxytocin receptor

The oxytocin receptor (OTR) is part of an ancient hormone system expressed in diverse phyla in relation to acute reproductive smooth muscle responses, such as egg-laying, birth, or milk letdown. The regulation of the OTR gene , while correlating with steroid levels in vivo, remains elusive. There app ear to be both inhibitory and stimulatory influences acting upon a constitu tive pattern of basal expression. We have found no evidence, however, for a n effect of the sex steroids either directly on gene transcription, or on t he receptor itself at the protein level. In the prostatic carcinoma cell li ne Du145, we have shown that up-regulation of the OTR gene transcription ca n be effected by cAMP. In an attempt to characterize the expression of the OTR protein in vivo, we ha we shown, using ligand-blotting, that the OTR ca n be expressed at different sizes in transfected cells and in myometrium. A lso, in the myometrium at term, immunohistochemistry suggests that there is both an increase in OTR protein per cell, as well as in the number of smoo th muscle cells expressing OTR, emphasizing that perinatal changes are the results of both individual gene activation events and gross cellular differ entiation. The OTR is a valuable model system reflecting molecular changes in the perinatal period. When we understand how this important molecule is regulated, we will also be a long way towards understanding the mechanisms controlling myometrial contractility at birth.