Interaction of Prostaglandin F_2α 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.

Regulation of Gonadotropin-Releasing Hormone (GnRH) Receptor-I Expression in the Pituitary and Ovary by a GnRH Agonist and Antagonist

“…GnRH-I is well known for its antiproliferative effects on granulosa cells of immature follicles, depression of steroid production, and promotion of ovum karyokinesis in mature follicles. [35][36][37][38][39][40][41][42] Under conditions in which CTX cytotoxicity activates cell growth, we speculated that GnRH-a inhibits follicular recruitment and follicle growth by depression of GnRHR-I expression in the pituitary, thus potentiating the GnRH-I effect in the ovarian compartment and conserving the follicle reserve. However, we found that GnRH-ant treatment stimulated significant expression of GnRHR-I in late growing follicles and antagonized GnRH-I inhibition of follicle growth through preservation of GnRHR-I, which consequently stimulates follicular recruitment and ulterior growth and exhausts the follicular reserve.…”

Mapping PTGERs to the Ovulatory Follicle: Regional Responses to the Ovulatory PGE2 Signal

“…PGE2 stimulated progesterone production by bovine cells from both small (<5mm) and large (>8mm) ovarian follicles while inhibiting estradiol secretion [ 164 ]. In human follicular fluid, elevated PGE2 concentrations correlated with elevated progesterone concentrations, and PGE2 increased STAR mRNA and protein as well as progesterone production by human granulosa-luteal cells in vitro [ 165 , 166 ]. Overall, these findings suggest that PGE2 may enhance progesterone synthesis by the ovulatory follicle or young corpus luteum.…”

PTGER1 and PTGER2 receptors mediate regulation of progesterone synthesis and type 1 11β-hydroxysteroid dehydrogenase activity by prostaglandin E2 in human granulosa–lutein cells

“…The ability of PGE 2 to stimulate progesterone synthesis in human and non-human primate luteal cells, and in the widely used model of human granulosa–lutein cells, is well documented (Hahlin et al 1988, Fehrenbach et al 1999, Vaananen et al 2001). Given the reported ability of PGE 2 to increase intracellular cAMP concentrations in these cells (Michael et al 1993) and the established role for cAMP as a second messenger that stimulates steroidogenesis (Cooke 1999), it has widely been assumed that the progesterone response to PGE 2 is mediated via this cyclic nucleotide.…”