Regulation of the Corpus Luteum by Protein Kinase C. II. Inhibition of Lipoprotein-Stimulated Steroidogenesis by Prostaglandin F_2α

Abstract

This study was designed to examine the antisteroidogenic action of prostaglandin (PG) F_2α on ovine luteal cells in vitro. Purified populations of large and small steroidogenic luteal cells were treated with lipoproteins, luteinizing hormone (LH), and/or PGF_2α. To investigate the involvement of the protein kinase C (PKC) pathway in hormone action, luteal cells were made PKC-deficient by treatment for 12 h with 1 μM phorbol-12-myristate-13-acetate. Progesterone production by nonstimulated large and LH-stimulated small luteal cells was significantly increased by treatment with high- and low-density lipoprotein (HDL, 5-fold increase; LDL, 2-fold increase). PGF_2α inhibited (p < 0.0001) progesterone production by HDL-stimulated large luteal cells in a dose-dependent manner, with 60 nM causing maximal inhibition. No effect of PGF_2α (20nM-20 μM) was found on production of progesterone by HDL-stimulated, PKC-deficient large cells or by LH- and HDL-stimulated small luteal cells. These results suggest that PGF_2α has a direct antisteroidogenic effect on the large luteal cell that is mediated through the PKC second messenger pathway.