In vitro conversion of estradiol-17beta into estrone in normal human myometrium and leiomyoma

Abstract

The specific activity of 17beta-hydroxysteroid dehydrogenase was measured in normal human myometrium, and in leiomyoma specimens obtained from the same tumor-bearing uterus. In all cases the normal tissue showed greater conversion of estradiol-17beta into estrone than the neoplastic tissues. In normal myometrium of fertile women, the specific enzyme activity depended on the phase of the menstrual cycle, the highest values of 17beta-hydroxysteroid dehydrogenase activity being found in the early secretory phase. To determine the intracellular distribution of the 17beta-hydroxysteroid dehydrogenase, purified microsomes, mitochondria, nuclei and cytosol fractions were prepared. The purity of each fraction was monitored by marker enzymes. It was found that the enzyme was mainly located in mitochondria and microsomes. Furthermore it was demonstrated that the microsomal enzyme was bound tightly to the membranes of the endoplasmic reticulum, while the mitochondrial 17beta-hydroxysteroid dehydrogenase was mainly associated with the outer membranes of the organelle. Kinetic parameters (Km-values, coenzyme requirements, temperature and pH-optima) of the cytoplasmic, nuclear, mitochondrial and microsomal enzyme of normal and neoplastic tissue were compared.