COMPOUNDS WITH ANTIESTROGENIC ACTIVITY IN VITRO1

Abstract

THE human placenta contains a DPN-linked isocitric dehydrogenase which is stimulated by the addition of estradiol in vitro (1–4). The enzyme was localized in the non-particulate fraction of homogenized placenta by differential ultracentrifugation in 0.25 M sucrose (2). Evidence that the estrogen-sensitive enzyme is isocitric dehydrogenase came from experiments with each of the tricarboxylic acids as substrates and with trcms-aconitate and fluorocitrate as specific enzyme inhibitors (3). Further experiments showed that estrone, equilin and equilenin have the same enzyme-stimulating property possessed by estradiol-17β. However, a great many other compounds tested, including estradiol-17α, estriol, progesterone, 17α-ethinylestradiol, testosterone, 19-nortestosterone, stilbestrol, cortisone, cortisol, and cholesterol, had little or no effect, no more than one one-thousandth as much as estradiol-17β (5). The results of kinetic experiments with this system are consistent with the hypothesis that estradiol unites with the protein to convert an enzymatically inactive form to an active form (6, 7).