Prostaglandin receptors and role of G protein-activated pathways on corpora lutea of pseudopregnant rabbit in vitro

Abstract

Studies were conducted to characterize receptors for prostaglandin (PG) F2α (PGF2α) and PGE2, and the signalling pathways regulating total nitric oxide synthase activity and progesterone production in rabbit corpora lutea (CL) of different luteal stages. CL were obtained at days 4, 9 and 13 of pseudopregnancy and cultured in vitro for 2 h with PGF2α or PGE2 and with activators and inhibitors of G protein (Gp), phospholipase C (PLC), protein kinase C (PKC), adenylate cyclase (AC) and protein kinase A (PICA). High affinity PGF2α receptor (Kd = 1.9 ± 0.6 nM mean ± S.E.M.) concentrations increased (P≤0.01) four-to five-fold from early to mid- and late-luteal phases (50.6 ± 8.5, 188.3 ± 36.1 and 231.4 ± 38.8 fmol/mg protein respectively). By contrast, PGE2 receptor (Kd= 1.6 ± 0.5 nM) concentrations decreased (P≤0.01) from day 4 to day 9 and 13 (27.5 ± 7.7, 12.4 ± 2.4 and 16.5 ± 3.0 fmol/mg protein respectively). The Gp-dependent AC/PKA pathway was triggered only on day 4 CL, mimicking the PGE2 treatment and increasing progesterone production. In both day 9 and day 13 CL, the Gp-activated PLC/PKC pathway evoked a luteolytic effect similar to that induced by PGF2α. The time-dependent selective resistance to PGF2α and PGE2 by rabbit CL is mediated by factors other than a lack of luteal receptor-ligand interactions.