In the rat, the respiration (but not the glycolysis) of slices of the ventral prostate gland falls to about 60 per cent of its normal value within 72 hours after castration and is restored to normal levels by the administration of testosterone (148). Stimulation of respiration by dinitrophenol was not affected very much by androgen deprivation. Longer periods after castration magnified the depression of oxygen consumption. Three days after orchiectomy, the respiration-coupled incorporation of acetate into long chain fatty acids was decreased to a greater extent than the respiration. But the entry of P32-labeled inorganic phosphate into the phospholipids, nucleic acids, and phosphoproteins of prostate slices under aerobic conditions was hardly changed by castration. Under a wide variety of experimental conditions, the respiration, glycolysis, and respiration-coupled synthetic reactions of isolated prostatic tissue were not influenced by the in vitro addition of androgenic steroids except at very high concentrations (>5 X 10^-5 M), where non-specific inhibitory effects were observed.

Mitochondria were isolated from the prostate gland and seminal vesicle (194, 191a, 200a). These particles catalyzed the aerobic oxidation of all members of the tricarboxylic acid cycle and of glutamate. The oxidation of these substrates was coupled with dinitrophenol-sensitive phosphorylations, as indicated by the uptake of inorganic phosphate in the presence of hexokinase and fructose, or by the incorporation of inorganic P32 into the phospholipids and phosphoproteins of the particles. The dephosphoryla-tion of adenosine polyphosphates by the prostate particles was very rapid, but there was little breakdown of added pyridine nucleotides. However, the particles isolated from accessory glands resembled tumor mitochondria inasmuch as the rate of oxidation of all substrates except succinate was very low without the addition of DPN, and citrate and isocitrate oxidation showed a marked requirement for TPN as well. In properly fortified preparations, the rate of oxidation of citrate was about the same as the rate of citrate synthesis from pyruvate and oxalacetate. The isocitric dehydrogenase of prostate mitochondria was shown to be absolutely specific for TPN. The aerobic oxidation of TPNH by these particles was much slower than that of DPNH, and the activity of the particulate transhydrogenase was low. None of the oxidations catalyzed by the accessory gland mitochondria were affected by the addition of low levels of sex hormones in vitro. Certain phenolic estrogens (e.g., diethylstilbestrol) uncoupled oxidative phosphorylation by prostate mitochondria, but there was no correlation between uncoupling and estrogenic activities. The oxidation of pyruvate and of citrate by fortified prostate mitochondria declined markedly within 48 hours after castration, and to a greater extent than succinate oxidation. These changes could be reversed by the administration of testosterone in vivo but not in vitro.

Small cytoplasmic particles (microsomes) which were isolated from the seminal vesicle were found to possess an active DPNH oxidase system. This DPNH oxidase was different from the mitochondrial electron transport system and was inhibited strongly by the in vitro addition of testosterone and certain other androgenic steroids. The rate of oxidation of TPNH by these microsomes was very low. The enzymatic pathways involved in the rapid and extensive degradation of TPN (H) and DPN(H) by prostate and seminal vesicle microsomes were studied in detail (2000).

The levels of 10 soluble pyridine nucleotide-linked dehydrogenases in the ventral prostate and coagulating glands were studied in normal and castrated rats (cf. 191). The most pronounced effects of androgen deprivation were a depression of the activity of malic dehydrogenase and an increase in the levels of lactic dehydrogenase; many TPN-linked enzymes were barely changed after castration. The activity of the soluble, TPN-spe-cific isocitric and glucose-6-phosphate dehydrogenases in the ventral prostate was such that the catalysis by these enzymes of citrate synthesis from α-ketoglutarate, CO2, and glucose-6-phosphate (in the presence of catalytic levels of TPN) was sufficiendy fast to account for the rates of citrate secretion by this gland. The androgen-dependent accumulation of citrate in the ventral prostate may, perhaps, be related to the latter reactions as well as to the feeble activity of enzymes catalyzing the aerobic oxidation of TPNH, which may serve to brake the mitochondrial oxidation of citrate. Androgen-dependent transhydrogenase reactions could not be demonstrated in the accessory glands.