Inactivation of prostaglandins in human decidua vera (parietalis) tissue: Substrate specificity of prostaglandin dehydrogenase

Abstract

Prostaglandin dehydrogenase catalyzes the initial reaction in the inactivation of prostaglandin E2 and F2 alpha. To address the potential importance of this enzyme in regulating the tissue levels of active prostaglandins, we evaluated the kinetic properties of prostaglandin dehydrogenase in uterine decidua vera tissue of women. Specifically, we characterized the enzyme activity under optimal in vitro conditions in cytosolic fractions of uterine decidua vera tissue obtained at term and compared the substrate and cosubstrate specificities of prostaglandin dehydrogenase in cytosolic fractions of decidual tissues. The incubation conditions were optimized with either prostaglandin E2 or F2 alpha and nicotinamide-adenine dinucleotide or nicotinamide-adenine dinucleotide phosphate as substrates to ensure linearity of product formation with time of incubation and protein concentration. The apparent Michaelis-Menten constant of nicotinamide-adenine dinucleotide-dependent prostaglandin dehydrogenase for prostaglandin E2 was 5.5 mumol/L. The apparent Michaelis-Menten constant of nicotinamide-adenine dinucleotide phosphate-dependent prostaglandin dehydrogenase for prostaglandin F2 alpha was 15 mumol/L. Prostaglandin E2 serves as a better substrate for prostaglandin dehydrogenase than does prostaglandin F2 alpha, irrespective of the cosubstrate. In cytosolic fractions of decidual tissues, the specific activity (apparent Vmax) of nicotinamide-adenine dinucleotide-dependent prostaglandin dehydrogenase was greater than that of nicotinamide-adenine dinucleotide phosphate-dependent prostaglandin dehydrogenase. In addition, we found that in decidual tissue obtained before or after the onset of labor, the specific activity of prostaglandin dehydrogenase varied widely. In tissues obtained after delivery by cesarean section, no significant differences were apparent in the specific activity of the enzyme before (9.3 to 125.8 nmol/min/mg protein) and after (27.8 to 103.4 nmol/min/mg protein) the onset of labor. In cytosolic fractions of decidual tissue obtained after vaginal delivery, the specific activity of nicotinamide-adenine dinucleotide-dependent prostaglandin dehydrogenase ranged from undetectable levels to 38.4 nmol/min/mg protein. We speculate that nicotinamide-adenine dinucleotide-dependent prostaglandin dehydrogenase in decidua serves to regulate the levels of bioactive prostaglandins in decidua vera tissue and the amounts of prostaglandins (and metabolites) produced in decidua or fetal membranes that reach myometrium and fetal membranes and enter maternal blood and amniotic fluid.