Activation-inactivation of hormone binding sites of the oestradiol-17 beta receptor is a multiregulated process

The calf uterus oestradiol-17 beta receptor exists in a hormone binding form, which is phosphorylated on tyrosine, and in a non-hormone binding form, which is dephosphorylated. Two enzymes regulate the number of hormone binding sites of the receptor: a kinase which has been purified from cytosol and a phosphatase purified from nuclei. Recent and new findings on the regulation of this activation-inactivation process are reported. In vitro only a fraction (30-60%) of the receptor binding sites are inactivated by the phosphatase. Evidence is given suggesting that this is due to the production during the inactivation process of a powerful inhibitor of the phosphatase. Ca2+-calmodulin stimulates the kinase activity with a parallel increase of phosphorylation on tyrosine and hormone binding sites of the receptor. Nanomolar concentrations of oestradiol-17 beta also stimulate the kinase to activate hormone binding sites. These results suggest that in intact cells inactivation-activation of the oestradiol receptor is a multiregulated process.