Interaction of Prostaglandin F2α and Prostaglandin-E2 on Progesterone Production in Human Granulosa-Luteal Cells

Abstract

This study examined the effects of prostaglandin-F_2α (PGF_2α), prostaglandin-E₂ (PGE₂) and their interactions on progesterone production in human granulosa-luteal cells (GLCs). Human GLCs collected from in vitro fertilization patients were cultured for 1 (D₁) or 8 days (D₈), followed by a 24-hour treatment period, after which media were collected and radioimmunoassayed for progesterone. Seven-point PGF_2α and PGE₂ concentration-response curves were crossed into a matrix of 49 separate treatments. Responses were plotted in three dimensions and as two-dimensional ‘slices’. In D₁ cultured human GLCs neither PGF_2α nor PGE₂ alone had any effect on progesterone production, however two different combinations of these hormones led to at least a 3-fold increase in progesterone production. This stimulation was seen when cells were treated with 10^–6M PGF_2α plus 10^–9M PGE₂, and when they were treated with 10^–10M PGF_2α plus 10^–9M PGE₂. In D₈ GLCs, PGF_2α stimulated progesterone production maximally at 10^–9M, while the lowest (10^–11 M) and highest concentrations (10^–6 M) tested were ineffectual. On the contrary, in the presence of high concentrations of PGE₂ (10^–6 to 10^–7 M), PGF_2α-mediated stimulation of progesterone production was attenuated. In a similar fashion to PGF_2α, PGE₂ also acted in a luteotrophic manner, although the maximal stimulation of progesterone production was seen at a higher concentration (10^–8 to 10^–7 M). Likewise, PGE₂-mediated progesterone production was attenuated by the presence of high concentrations of PGF_2α (10^–6 to 10^–7 M). In conclusion, in D₁ human GLCs neither PGF_2α nor PGE₂ alone were luteotrophic, although specific combinations of these hormones were. Conversely, in D₈ GLCs both PGF_2α and PGE₂ stimulated progesterone production in a biphasic manner, while the presence of a high concentration of either of these prostaglandins attenuated the luteotrophic effects of the other. Therefore, PGF_2α and PGE₂ interacted in a concentration-dependent manner, resulting in a multimodal progesterone response, which was easily visualized using three-dimensional plots.