Disactivation and Inhibition of Activation of the Estrogen Receptor from Chick Oviduct by Periodate - Comparison with the Effects of Molybdate and O-Phenanthroline

Abstract

A series of compounds was tested for the inhibition of binding of the estradiol-receptor complex from chick oviduct to DNA. Most of the inhibitory substances were also found to elute bound receptor complex from DNA. Only a few had inhibitory properties without an eluting capacity. One of these compounds is periodate which, to our knowledge, has not been studied up to now as an inhibitor of steroid hormone receptors. Therefore, we investigated the effects of periodate on the estrogen-receptor complex in more detail and compared them to those of the two known inhibitors, molybdate and o-phenanthroline. Periodate reacts irreversibly with the non-activated estrogen receptor from chick oviduct and blocks activation. It also affects the activated form of the receptor causing an irreversible loss of its DNA binding ability. This process is termed disactivation. Molybdate is able to inhibit the temperature, as well as the salt induced activation in a reversible manner. However, it cannot disactivate the active form of the receptor. In contrast, o-phenanthroline appears to be unable to influence the activation process i.e. to react with the non-activated form of the receptor, but instead disactivates the activated receptor. The simultaneous determination of alkaline phospha-tase inhibition by some of the tested compounds did not allow to decide if a dephosphorylation step is required for the activation of the estrogen receptor.