Summary
The transformation of progesterone into four more polar metabolites was investigated using liver microsomes from untreated as well as phenobarbitaltreated rabbits. The formation of the four metabolites was dependent on oxygen and NADPH. The reactions were inhibited by CO and this inhibition by CO was partially reversible by light. The four reactions had the same pH-optimum at 7.4.
The metabolite pattern was not changed by reducing the oxygen pressure, by inhibiting the reactions with CO, by diminishing the CO effect by light, by variation of the pH value, by separating microsomes into smooth and rough membranes, or by increasing the specific enzyme activities by a factor of 1.5, as a result of treating the microsomes by freezing, thawing, and consecutive centrifugation or filtration on agarose gel.
Phenobarbital-treatment of the animals increased the formation of the four metabolites to different degrees, i.e. 3, 1.4, 15, and 6 fold, respectively. Since this procedure was the only one which changed the metabolite pattern, this effect is easier to explain by effects of the phenobarbital-treatment on the rate-limiting steps of the four reactions than by the assumption of four different enzymes catalyzing the metabolism of progesterone.
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Ein Teil der Ergebnisse wurde auf der 10. Frühjahrstagung der Deutschen Pharmakologischen Gesellschaft in Mainz (1969) vorgetragen.
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Lange, G., Thun, K.J. Hydroxylierung von Progesteron durch Lebermikrosomen von Kaninchen. Naunyn-Schmiedebergs Arch. Pharmak. 267, 265–277 (1970). https://doi.org/10.1007/BF00997097
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DOI: https://doi.org/10.1007/BF00997097