Etude du métabolisme du 3-propyl-éther de l'estradiol 17β comparativement à l'estradiol 17β dans le foie de rat perfusé

Abstract

The metabolism of 6,7-3H-tabelled 3-propyl ether estradiol (PE2) and of [6,7-3H]estradiol was studied by rat liver perfusion under different experimental conditions. In all cases, 90% of the radioactivity was retained in the liver, indicating an active uptake by the liver. The hepatic radioactivity was slowly released at a constant rate in the efferent perfusate. The proportion of radioactive metabolites in the perfusate was approximately the same as in the liver.3-Propyl ether estrone (PE1), a dehydrogenation product of PE2, and 3-propyl ether estriol (PE3), a 16α-hydroxylated derivative of PE2, were identified. Propylated metabolites more polar than PE2 were found. A low amount of propylated metabolites was conjugated with the exception of PE1. From the appearance of phenolic steroids including estrone, estradiol, and estriol, it was concluded that cleavage of the 3-propyl ether group had occurred.Compared with perfusion under oxygen, the overall metabolism was significantly reduced when the perfusion was carried out under nitrogen which demonstrates that oxygen plays a part in all the enzymatic systems involved. When animals were stimulated by phenobarbital, their entire metabolism was activated. These results suggest a metabolism mainly located in the hepatic microsomes.Our results show that the propylated hormone is metabolized like the free hormone. However, the transformations of PE2 are slower when compared with estradiol: thus, the 3-propyl ether group provided some hormone protection against hepatic degradation.