Interaction of prostaglandin F(2alpha) and prostaglandin E(2) on progesterone production in human granulosa-luteal cells.
This study examined the effects of prostaglandin-F(2alpha) (PGF(2alpha)), prostaglandin-E(2) (PGE(2)) and their interactions on progesterone production in human granulosa-luteal cells (GLCs). Human GLCs collected from in vitro fertilization patients were cultured for 1 (D(1)) or 8 days (D(8)), followed by a 24-hour treatment period, after which media were collected and radioimmunoassayed for progesterone. Seven-point PGF(2alpha) and PGE(2) concentration-response curves were crossed into a matrix of 49 separate treatments. Responses were plotted in three dimensions and as two-dimensional "slices". In D(1) cultured human GLCs neither PGF(2alpha) nor PGE(2) 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(-6) M PGF(2alpha) plus 10(-9) M PGE(2), and when they were treated with 10(-10) M PGF(2alpha) plus 10(-9) M PGE(2). In D(8) GLCs, PGF(2alpha) stimulated progesterone production maximally at 10(-9) M, 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 PGE(2) (10(-6) to 10(-7) M), PGF(2alpha)-mediated stimulation of progesterone production was attenuated. In a similar fashion to PGF(2alpha), PGE(2) 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, PGE(2)-mediated progesterone production was attenuated by the presence of high concentrations of PGF(2alpha) (10(-6) to 10(-7) M). In conclusion, in D(1) human GLCs neither PGF(2alpha) nor PGE(2) alone were luteotrophic, although specific combinations of these hormones were. Conversely, in D(8) GLCs both PGF(2alpha) and PGE(2) 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(2alpha) and PGE(2) interacted in a concentration-dependent manner, resulting in a multimodal progesterone response, which was easily visualized using three-dimensional plots.
Väänänen
J E
JE
Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, B.C., Canada.
Tong
B L
BL
Väänänen
C C
CC
Chan
I H
IH
Yuen
B H
BH
Leung
P C
PC
D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D015237:Dinoprost / Q000008:administration & dosage*; D015232:Dinoprostone / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008184:Luteal Cells / Q000187:drug effects* / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects
D011374:Progesterone; D004247:DNA; D015237:Dinoprost; D015232:Dinoprostone