Prostaglandin E-2 (PGE(2)) exerts mainly luteotrophic effects in the corpus luteum. In other tissues, PGE,, acts via specific PGE2 receptor subtypes including EP1, which modulates intracellular calcium ([Ca2+](i)) and EP2, which is coupled to cyclic AMP (cAMP) generation. We have therefore investigated the presence of functional EP1 and EP2 receptors using human granulosa-lutein (GL) cells. Reverse-transcription PCR revealed that GL cells expressed mRNA transcripts encoding both EP1 and EP2 receptors. When GL cells were challenged with ligands that can bind to both receptor subtypes (PGE2 and 16,16 dimethyl PGE) or exclusively to EP2 (butaprost), both cAMP formation and progesterone synthesis were stimulated. Furthermore, the cAMP response to these agonists could be significantly blocked by an EP1/2 antagonist AH6809 but not by an EP1-selective antagonist SC19220. Exposure of GL cells to 16,16-dm PGE(2) transiently raised [Ca2+](i) levels, which could be prevented by both AH6809 and SC19220. We therefore conclude that human GL cells express functional EP1 and EP2 receptors.