REGULATION OF PROSTAGLANDIN-F2-ALPHA RECEPTOR EXPRESSION IN CULTURED HUMAN GRANULOSA-LUTEAL CELLS

PGF(2 alpha) is a metabolite of arachidonic acid that triggers regress ion of the corpus luteum. Recent animal studies have indicated that PG F(2 alpha) (FP) receptor messenger ribonucleic acid (mRNA) is expresse d in the corpus luteum. To understand the regulation of the FP recepto r in the ovary we have cloned a partial complementary DNA (cDNA) seque nce of the FP receptor from human granulosa cells obtained from women undergoing in vitro fertilization. The sequence of this cDNA is identi cal to the previously reported FP receptor sequences obtained from hum an uterine and placental cDNA libraries. Low levels of the FP receptor mRNA were observed in freshly isolated granulosa cells or in cultured granulosa-luteal (GL) cells, as detected by reverse transcriptase-PCR . hCG and 8-bromo-cAMP increased the steady state levels of the FP rec eptor mRNAs after incubation for 24-38 h, as detected by Northern blot hybridization. The stimulatory effect of hCG was concentration and cu lture stage dependent. Further, hCG and 8-bromo-cAMP increased binding of radiolabeled PGF(2 alpha) to intact GL cells. In contrast, phorbol 12-myristate 13-acetate inhibited basal as well as hCG- and 8-bromo-c AMP-induced FP receptor mRNA expression and binding of the radiolabele d ligand. In summary, hCG, 8-bromo-cAMP, and phorbol 12-myristate 13-a cetate modulate the expression of the FP receptor in human GL cells, w hich may represent a mechanism to regulate the responsiveness of the o vary to PGF(2 alpha).