An increase of both gap junction formation and oxytocin receptor number is indeed observed in myometrial cells, together with the stimulation of oxytocin gene expression in human choriodecidua in addition, estrogens modulate prostaglandin (PG) production by intrauterine tissues. The consequent enhancement in the local estrogen/progesterone ratio may exert several actions aimed at preparing the uterus for delivery. Human intrauterine tissues also synthesize estrogens that are at higher levels around the time of parturition, and concomitantly, a decrease of progesterone occurs. Fetal membranes and maternal decidua are sources for these compounds, whose release increases during the progression of pregnancy. Several factors are likely involved, among these oxytocin and prostaglandins, because they are able to evoke myometrial contractions. The mechanisms responsible for the initiation of human parturition are still poorly understood. The nucleotide is presumably responsible for the enhacement of hormone receptor availability and for the inhibition of PGE 2 release observed in the presence of Ro 20-1724. Our data demonstrate for the first time that 1) 17β-estradiol modulates PGE 2 release from WISH cells, interacting with specific intracellular receptors and probably evoking new protein synthesis, and 2) WISH cell responsiveness to 17β-estradiol seems to be modulated by cAMP, whose levels are significantly increased by the steroid hormone in the presence of Ro 20-1724. Both stimulatory and inhibitory actions are inhibited by the estrogen receptor antagonist, tamoxifen, by cell pretreatment with cycloheximide, or when the hormone is bound to BSA. In cells unexposed to these drugs, 17β-estradiol stimulates prostaglandin (PG)E 2 release but exerts an evident inhibitory effect in cells exposed to Ro 20-1724. In human amnion-derived WISH cells estradiol-17β binding sites are not detectable, but they become measurable in cells exposed to cAMP elevating agents such as forskolin or Ro 20-1724.