Intraluteal regulation of prostaglandin F2α-induced prostaglandin biosynthesis in pseudopregnant rabbits

Abstract

The objective of the present study was to investigate in rabbit corpora lutea (CL), at both the cellular and molecular level, intraluteal cyclooxygenase (COX)-1, COX-2 and prostaglandin (PG) E2-9-ketoreductase (PGE2-9-K) enzymatic activities as well as in vitro PGE2 and PGF2α synthesis following PGF2α treatment at either early- (day-4) or mid-luteal (day-9) stage of pseudopregnancy. By immunohistochemistry, positive staining for COX-2 was localized in luteal and endothelial cells of stromal arteries at both the stages. In CL of both stages, basal COX-2 mRNA levels were poorly expressed, but rose (P<0.01) 4- to 10-fold 1.5-6 h after treatment and then gradually decreased within 24 h. Compared to mid-stage, day-4 CL had lower (P<0.01) COX-2 and PGE2-9-K basal activities, and PGF2α synthesis rate, but higher (P<0.01) PGE2 production. Independent of luteal stage, PGF2α treatment did not affect COX-1 activity. In day-4 CL, PGF2α induced an increase (P<0.01) in both COX-2 activity and PGF2α synthesis, whereas that of PGE2 remained unchanged. In day-9 CL, PGF2α up-regulated (P<0.01) both COX-2 and PGE-9-K activities, and PGF2α production, but decreased (P<0.01) PGE2 synthesis. All changes in gene expression and enzymatic activities occurred within 1.5 h after PGF2α challenge and were more marked in day-9 CL. Our data suggest that PGF2α directs intraluteal PG biosynthesis in mature CL, by affecting the CL biosynthetic machinery to increase the PGF2α synthesis in an auto-amplifying manner, with the activation of COX-2 d PGE-9-K; this may partly explain their differentially, age-dependent, luteolytic capacity to exogenous PGF2α in rabbits. © 2007 Society for Reproduction and Fertility.