title: Mitochondria from human term placenta. III. The role of respiration and energy generation in progesterone biosynthesis.
abstract: The interrelationships among the processes of progesterone biosynthesis, respiration and energy production in human term placental mitochondria were examined. All substrates (citrate, isocitrate, alpha-ketoglutarate, succinate, fumarate, malate, glutamate, glycerol 3-phosphate, ascorbate + N,N,N',N'-tetramethyl-p-phenylenediamine) previously found to stimulate oxygen uptake and ATP synthesis in placental mitochondria supported progesterone synthesis from endogenous and exogenous cholesterol. Citrate support of progesterone synthesis was stimulated by NADP+ but not NAD+. It was inhibited by fluorocitrate and trans-aconitate but not by arsenite, rotenone, antimycin, cyanide or 2,4-dinitrophenol. Ascorbate-N,N,N',N'-tetramethyl-p-phenylenediamine support of progesterone synthesis was stimulated by NAD+ and NADP+ and was inhibited by ADP, rotenone, antimycin, cyanide and 2,4-dinitrophenol. Cyanide inhibition was relieved by an exogenous ATP regenerating system and ADP inhibition was reversed by oligomycin. Progesterone synthesis supported by alpha-ketoglutarate + malonate was stimulated by NAD+ and NADP+, and was completely inhibited by arsenite. 2,4-Dinitrophenol was strongly inhibitory both in the absence and presence of rotenon or antimycin. Stimulation by ATP was enhanced by rotenon, antimycin and oligomycin and inhibited by 2,4-dinitrophenol. Thus, metabolic control of progesterone synthesis by the energy status of the mitochondrial system was demonstrated when reducing equivalents were supplied via NADH or the respiratory electron transport chain.
mesh_terms: D002784:Cholesterol / Q000378:metabolism; D002952:Citric Acid Cycle; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D007656:Ketoglutaric Acids / Q000378:metabolism; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism; D010101:Oxygen Consumption; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000096:biosynthesis*
chemical_list: D007656:Ketoglutaric Acids; D011374:Progesterone; D002784:Cholesterol