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

The objective was to investigate, both on cellular and on molecular level, the role of key enzymes for the prostaglandin (PG) biosynthesis in modulating PGF2a?-induced corpora lutea (CL) regression in the early- and mid-luteal stage of pseudopregnancy, at days 4 and 9, respectively. By immunohistochemistry, strong positive staining for cyclooxygenase-2 (COX-2) was localized in luteal and endothelial cells at both stages, 3 h after PGF2a injection. In CL of both stages, basal COX-2 mRNA levels were poorly expressed, but rose (p £ 0.01) 20- to 50-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, PGF2a synthase (PGFS) and PGE2-9-ketoreductase (PGE-9-K) basal activities, but higher (p £ 0.01) PGE2 synthase (PGES) activity. Independently of luteal stage, PGF2a treatment did not cause any change in COX-1 activity. In d-4 CL, PGF2a induced an increase (p £ 0.01) in both COX-2 and PGFS activity, whereas that of PGES remained unchanged. Conversely, in d-9 CL, PGF2a up-regulated (p £ 0.01) the activity of COX-2, PGFS, and PGE-9-K, but decreased (p £ 0.01) that of PGES. All changes in gene expression and enzymatic activities occurred within 1.5 h after PGF2a challenge and were more marked in d-9 CL. Our data suggest that PGF2a directs the intraluteal PG biosynthesis differently in growing and mature CL, thus partly explaining their age-dependent responsiveness to exogenous PGF2a in rabbits