Human Progesterone Receptors Have Two Intracellular Hormone Binding Proteins That Are Covalently Modified in Nuclei

Abstract

Progesterone receptors (PR) are believed to be gene-regulatory proteins by virtue of their ability to bind chromatin and DNA. Neither the structural organization nor the nuclear sites of action of these proteins is resolved. The questions that persist include the size and number of hormone-binding subunits of the holoreceptors and the means by which receptors are transformed* to tight chromatin-binding proteins in response to hormone treatment. With regard to the number of hormone-binding forms, two proteins of different molecular weight have been described for chick oviduct and human breast cancer PR, and two molecular weight forms are occasionally seen for estrogen, glucocorticoid, and Vitamin D3 receptors as well (reviewed in Horwitz et al., 1985a). However, it is generally argued that for all these receptors, smaller molecular weight proteins are proteolytic artifacts formed during in vitro incubations (Loosfelt et al., 1984). Questions also persist about the mechanisms by which progesterone converts the receptors from loose to tight chromatin-binding proteins, and virtually nothing is known about the means by which the actions of the nuclear hormone-receptor complexes are terminated.