Gonadotropin-induced expression of messenger ribonucleic acid for cyclooxygenase-2 and production of prostaglandins E and F2alpha in bovine preovulatory follicles are regulated by the progesterone receptor.
Follicular production of prostaglandins (PGs) is essential for ovulation, but the factors mediating gonadotropin-induced secretion of PGE and PGF(2alpha) remain largely unknown. We tested the hypothesis that gonadotropin-induced changes in progesterone and its receptor (PR) mediate the increase in periovulatory PGs. Heifers were treated with PGF(2alpha) and GnRH to induce luteolysis and the LH/FSH surge (ovulation occurs approximately 30 h after GnRH). Because there are two increases in intrafollicular progesterone/PR mRNA during the bovine periovulatory period, we first examined the temporal pattern of PG production by follicles collected at 0, 3.5, 6, 12, 18, and 24 h after GnRH. Although PGs did not increase in the follicular fluid until 24 h after GnRH, acute secretion of PGs by follicle wall (theca + granulosa cells) was initiated by 18 h and had increased manyfold by 24 h after GnRH. In vitro, FSH and LH induced dramatic transient increases in PG production by follicle wall and granulosa, but not theca, cells isolated from preovulatory follicles (0 h after GnRH). PG accumulation peaked on d 2 of culture, mimicking the secretion pattern after a gonadotropin surge in vivo. In cultures of follicle wall and granulosa cells, the PR antagonist mifepristone (MIFE, 1 microm) inhibited LH-induced PG secretion and the progestin medroxyprogesterone acetate (1 or 10 microm), but not the glucocorticoid dexamethasone (1 or 10 microm), overcame the effect of MIFE on PGs. Semiquantitative RT-PCR revealed that MIFE inhibited LH-induced expression of cyclooxygenase-2 mRNA in granulosa cells in vitro. Again, treatment with medroxyprogesterone acetate overcame the effect of MIFE. Together these results provide strong evidence that periovulatory increases in cyclooxygenase-2 mRNA, PGE, and PGF(2alpha) are mediated by gonadotropin-induced increases in progesterone/PR, indicating that in some species there is an important functional relationship between these pathways in the ovulatory cascade.
Bridges
P J
PJ
Department of Biomedical Sciences, Cornell University, Ithaca, New York 14853, USA.
Komar
C M
CM
Fortune
J E
JE
D000818:Animals; D002417:Cattle; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D015237:Dinoprost / Q000096:biosynthesis*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D006062:Gonadotropins / Q000494:pharmacology*; D006107:Granulosa Cells / Q000378:metabolism; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000494:pharmacology; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism*; D010060:Ovulation / Q000502:physiology; D011458:Prostaglandins E / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D011863:Radioimmunoassay; D011980:Receptors, Progesterone / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013799:Theca Cells / Q000187:drug effects / Q000378:metabolism
D006062:Gonadotropins; D011458:Prostaglandins E; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D015237:Dinoprost; D051546:Cyclooxygenase 2