Localization and functions of steroid hormone receptors

Abstract

This review focuses on the subcellular localization of steroid hormone receptors (SHRs), taking into account the technical problems of immunohistochemistry and the characteristics of nuclear localization signals (NLSs) of each receptor, on the interaction between SHKs and cellular components, and on the possible roles of sex SHRs in the reproductive organs. It is concluded that SHRs are basically localized in the nucleus, regardless of hormonal status, and that considerable amounts of unliganded SHRs may be present in the cytoplasm of target cells in exceptional cases. Most immunohistochemical results that demonstrate nuclear translocation of liganded SHRs seem to be responsible for insufficient fixation. Immunoelectron microscopy shows that SHRs associate with the chromatin in absence or presence of hormones and that intranuclear translocation of liganded SHRs from the condensed chromatin to euchromatin which observed in some cell types, may be a passive process caused by a consequence of conformational changes in the chromatin binding receptors. Histochemical data suggest that the nuclear matrix (NM) is not a main binding site of liganded SHRs in the nucleus. The artificial formation of intermolecular disulfide bonds during NM preparation presumably causes the entrapment of liganded SHRs into the fraction. It seems that heat shock protein 90 (hsp90) does not form stable complexes with unliganded receptors in vivo, and it interacts with SHRs transiently cooperating with other heat shock proteins as a chaperone that helps folding of newly synthesized and refolding of denatured receptors. Estrogens transiently induce a number of nuclear protooncogenes, such as c-fos and c-jun family proteins, which act as transcription factors through estrogen receptor (ER) system in the endometrial epithelium of mature and immature rodents. Therefore, it is suggested that the changes in concentrations of these gene products trigger the proliferation and differentiation of uterine epithelium. In addition, ER system, not only in stroma cells but in the epithelia1 cells appears to participate in the growth response and abnormalities of epithelium elicited by the exogenous estrogen treatment at the neonatal period.