The structural specificity of the estrogen-sensitive enzyme system in placental homogenates.

Villee et al. (1, 2) have described a diphosphopyridine nucleotide-linked isocitric dehydrogenase system in human placenta which is stimulated by estradiol-170, estrone, equilin, and equilenin. The enzyme system is stimulated to a much lesser extent by estriol, progesterone, diethylstilbestrol, testosterone, I9-nortestosterone, 17a-ethinyl estradiol, and estradiol-17a. Recently, Williams-Aschman and Talalay have demonstrated that enhancement of isocitrate utilization by estradiol involves the coupling of isocitric dehydrogenase-triphosphopyridine nucleotide and a steroid-sensitive transhydrogenase which operates because of catalytic amounts of triphosphopyridine nucleotide present in the placental homogenate (3). The present paper reports the effects of various substituted estrogens and attempts to relate their structure with activity in this hormone dependent system.