Changes in progesterone receptor isoforms in cultured human uterine smooth muscle cells with pregnancy, mechanical stretch and labour at term

Abstract

There is no detectable progesterone withdrawal in maternal serum at the onset of parturition. However, antiprogestagens cause cervical ripening at term and may cause abortion at other gestations. Therefore, it is likely that withdrawal occurs at a cellular or receptor level. Oestrogen receptors (ER) regulate genes which cause myometrium to become contractile, whereas progesterone and its receptors (PR) are thought to contribute to quiescence. We demonstrate in this study that in cultured myocytes taken from lower segment biopsies at the time of caesarean section before or after labour or from hysterectomy specimens, receptor isoforms change, causing a functional progesterone withdrawal. There was no difference between PR isofroms from hysterectomy specimens and at term before labour. Although there was an increase in both PR-A and PR-B isoforms with labour, there was in increase in PR-A to -B ratio from 20 to 65. ER expression decreases and is almost undetectable during pregnancy. Myometrial cells stretched for 6 hours show that expression of PR-A remains unchanged, whereas PR-B is downregulated.