Reversible activation of non-steroid binding oestrogen receptor

Abstract

Two high-affinity oestrogen receptors have been identified in the chick oviduct with equilibrium dissociation constants (K_d) of 0.1 and 1 nM, differing in their binding kinetics, role in ovalbumin synthesis and independent regulation in vivo. The higher-affinity receptor (X) increases RNA polymerase II activity directly¹, whereas the low-affinity receptor (Y) seems to be necessary to confer specificity to transcription of oestrogen-dependent genes². Acute administration of progesterone to oestrogen-stimulated chicks results in preferential destruction of the nuclear Y receptor³ accompanied by interruption of ovalbumin gene transcription⁴. Here we demonstrate that receptor Y exists in a non-oestradiol binding form (Y_nb) which can be activated to the binding form in vitro by treatment with either ATP or ADP. Furthermore, dialysis of oviduct cytosol, which has no effect on the high-affinity receptor X, converts receptor Y to Y_nb; receptor Y can then be recovered by treatment with ATP in the presence of Mg²⁺ and independently of Ca²⁺. This is the first report of the controlled interconversion between a non-steroid binding form of oestrogen receptor and active receptor in a tissue that contains two independently regulated oestrogen receptor types.