Comparison of estrogen receptors in human premenopausal and postmenopausal uteri: indication of biologically inactive receptor in postmenopausal uteri.
Analysis of the estrogen receptor (ER) from uteri of premenopausal and postmenopausal patients has largely been limited to quantitation. The present study examined the biologic activity of the receptors with regard to their nuclear binding capacities. A Scatchard analysis of myometrial cytosol indicated high-affinity and low-capacity estradiol binding (Kd = 10(-10 M). A 35% ammonium sulfate fraction of cytosol was characterized for steroid specificity, receptor concentration, isoelectric focusing patterns, and capacity of the ER to bind to nuclear acceptor sites in a cell-free assay. The ER from premenopausal uteri displayed an extensive but saturable binding to the nuclear acceptor sites. In contrast, the postmenopausal ER displayed minimal binding. These cell-free binding differences were supported by tissue culture studies. This difference may be accentuated by the fact that much of the receptor is bound by endogenous estrogen in the premenopausal uterine preparation, which would decrease the subsequent binding of the [3H]ER to nuclear sites. This receptor in the postmenopausal uterus is largely unbound and thus would not compete for nuclear sites. These studies suggest that a significant fraction of the ER in postmenopausal uteri is biologically inactive; for example, it cannot translocate and bind to nuclear acceptor sites. This loss in nuclear binding may represent a change in the ER occurring at menopause as a result of changing endocrine states.
D000328:Adult; D000368:Aged; D002843:Chromatin / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006801:Humans; D007525:Isoelectric Focusing; D007526:Isoelectric Point; D008593:Menopause; D008875:Middle Aged; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000032:analysis / Q000378:metabolism*; D014599:Uterus / Q000032:analysis / Q000378:metabolism*
D002843:Chromatin; D011960:Receptors, Estrogen; D004958:Estradiol