Localization of prostaglandin F(2α) inhibition of lipoprotein use by bovine luteal cells

Abstract

Prostaglandin F(2α) (PGF(2α)) inhibits lipoprotein-stimulated progesterone production by bovine luteal cells in vitro and the objective of this study was to localized the site of action of PGF(2α). Cultured bovine luteal cells were treated with PGF(2α) for seven days, and then with either lipoproteins or 25-hydroxycholesterol in the presence of aminoglutethimide (which inhibits cholesterol side-chain cleavage) for the final 48 h. The effects of PGF(2α) on progesterone production, cellular cholesterol content, mitochondrial cholesterol content and cholesterol side-chain cleavage activity were determined. As expected, PGF(2α) inhibited (p < 0.05) lipoprotein-stimulated progesterone production. However, PGF(2α) did not inhibit low-density lipoprotein-stimulated, of high density lipoprotein-stimulated, increases in cellular cholesterol (p < 0.05) or inhibit lipoprotein-induced increases in mitochondrial cholesterol content (P < 0.05). Additionally, cholesterol content of mitochondria increased (p < 0.05) in the presence of PGF(2α) alone. To determine if the PGF(2α)-induced inhibition of steroidogenesis occurred at, or after, the side-chain cleavage reaction, we treated cells with the readily diffusable sterol, 25-hydroxycholesterol. Prostaglandin F(2α) did not inhibit 25-hydroxycholesterol-stimulated progesterone production (P < 0.05). Prostaglandin F(2α) may therefore exert its luteolytic effect at a site after cholesterol transport to the mitochondria but before cholesterol side-chain cleavage.