Biochemical cascade mediating the estradiol action.

The data suggest that estradiol enhances the formation of histamine in rat uterus by induction of histidine decarboxylase; histamine activates adenylate cyclase providing accumulation of cyclic 3',5'-AMP, which, probably, induces glycolytic enzymes via phosphorylation of chromatin proteins, and mediates other estradiol effects. The chain of successively acting enzymes and mediators constitutes, obviously, a cascade amplifying the estradiol action. Since histamine is known to act as an intercellular mediator, attempts were made to find out the distribution of estradiol, histamine, and cyclic 3',5'-AMP among uterine cells. Autoradiography has shown that 3H-estradiol is bound by the nuclei of myometrium cells, 3H-histamine was found in the cytoplasm of these cells, 3H-cyclic 3',5'-AMP is selectively bound by the cells of capillary endothelium of the uterus. The estradiol mediators seem to spread their effect on different types of cells which form together a kind of a multicellular functional system.