EXPRESSION OF 3-BETA-HYDROXYSTEROID DEHYDROGENASE-5,4-EN ISOMERASE ACTIVITY BY INFILTRATING DUCTAL HUMAN BREAST-CARCINOMA IN-VITRO

In order to determine whether human mammary tumors could contribute to progesterone synthesis from pregnenolone in breast cancer patients, h omogenates of infiltrating ductal primary breast tumors at different s tages of malignancy (Stages II and III) obtained from pre- and post-me nopausal patients (n = 7, age 37-66 years) were incubated with [7n-H-3 ]pregnenolone as substrate. Controls were heated homogenates instead o f fresh homogenates. With the use of reverse-isotope dilution analysis , [H-3]progesterone was isolated and characterized. No such metabolite was evident in the control incubations of heat-denatured enzymes. The extent of enzymic conversion varied from 0.02 to 4.0%. The results re veal that activity of 3 beta-hydroxysteroid dehydrogenase-5,4-en isome rase that metabolizes pregnenolone to progesterone can be identified w ith the viable homogenates. It is suggested that there exists a potent ial for substantial progesterone synthesis in vivo. This conversion ma y be of considerable clinical, therapeutic, and pathophysiological sig nificance in the patient with breast cancer. The biological impact of this conversion should be a high priority research objective.