Age-dependent intraluteal regulation of prostaglandin biosynthesis during PGF2-induced luteolysis in pseudopregnant rabbits

The objective was to investigate, both on cellular and on molecularlevel, the role of key enzymes for the prostaglandin (PG) biosynthesisin modulating PGF2a?-induced corpora lutea (CL) regression in theearly- and mid-luteal stage of pseudopregnancy, at days 4 and 9,respectively. By immunohistochemistry, strong positive staining forcyclooxygenase-2 (COX-2) was localized in luteal and endothelial cellsat both stages, 3 h after PGF2ainjection. In CL of both stages, basalCOX-2 mRNA levels were poorly expressed, but rose (p£0.01) 20- to50-fold 1.5 h after treatment and then gradually decreased within 24 h.Compared to mid-stage, d-4 CL had lower (p£0.01) COX-2, PGF2asynthase (PGFS) and PGE2-9-ketoreductase (PGE-9-K) basal activ-ities, but higher (p£0.01) PGE2 synthase (PGES) activity. Independ-ently of luteal stage, PGF2atreatment did not cause any change inCOX-1 activity. In d-4 CL, PGF2ainduced an increase (p£0.01) inboth COX-2 and PGFS activity, whereas that of PGES remainedunchanged. Conversely, in d-9 CL, PGF2aup-regulated (p£0.01) theactivity of COX-2, PGFS, and PGE-9-K, but decreased (p£0.01) thatof PGES. All changes in gene expression and enzymatic activitiesoccurred within 1.5 h after PGF2achallenge and were more marked ind-9 CL. Our data suggest that PGF2adirects the intraluteal PGbiosynthesis differently in growing and mature CL, thus partlyexplaining their age-dependent responsiveness to exogenous PGF2ain rabbits.