Prostaglandin F2-alpha receptor regulation in human uterine myocytes

Abstract

Investigations of the modulation of prostaglandin F2α receptor (FP) expression in primary cultures of human uterine myocytes showed that FP mRNA expression was reduced by progesterone, unaltered by cAMP (8-bromo cAMP or forskolin), but increased by the PKA antagonist H89. Interleukin (IL)-1β, tumour necrosis factor-alpha and oxytocin increased FP mRNA expression and IL-6 and prostaglandin E2 reduced FP mRNA expression. The changes in FP protein levels were similar to the mRNA responses. We found that the IL-1β-induced increase in FP expression was mediated at least in part via protein kinase C (PKC), but was independent of mitogen-activated protein kinase, phospholipase C and PI3 kinase. Since IL-1β activates NFκB, AP-1 and C/EBP, we over-expressed these transcription factors alone and in combination and found that only NFκB alone increased FP mRNA expression. Finally, we found that the IL-1β-induced increase in FP expression was unaffected by progesterone and/or cAMP, but was accentuated by H89. These data suggest that the pregnancy-induced down-regulation in myometrial FP expression is mediated by progesterone and cAMP and that the increase with labour is induced by inflammatory cytokine activation of PKC and NFκB. © The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.