Interactions between progesterone receptor isoforms in myometrial cells inhuman labour

Progesterone acts to maintain uterine quiescence during pregnancy. In contr ast to many other species, no decrease in maternal serum levels of progeste rone can be observed in humans before the onset of labour. Therefore, a 'fu nctional' progesterone withdrawal in association with labour has been propo sed. In humans the progesterone receptor (PR) exists in two isoforms, PR-A and PR-B. While PR-B generally mediates the effects of progesterone upon ge ne transcription, the role of PR-A during pregnancy, and in parturition, is unknown. In this study, term myometrium cells cultured before the onset of labour were transiently transfected with expression vectors for either PR- A or PR-B. Only those cells expressing PR-B significantly increased express ion of a progesterone-sensitive reporter when stimulated with progesterone. Co-transfection of both isoforms; of PR demonstrated that PR-A is a domina nt repressor of transactivation in these cells. Western blot analysis showe d that PR-A is present in human myometrium samples taken only after, but no t before, the onset of labour. These data suggest that increased expression of PR-A in human myometrium may contribute to 'functional' progesterone wi thdrawal and the initiation of human labour.