Isolation and characterization of an estrogen binding protein which may integrate the plethora of estrogenic actions in non-reproductive organs.
A putative estrogen receptor (pER) from mouse liver has been characterized. The heterodimer protein (81-84 kDa) consists of two covalently bound subunits (61-67 and 17-27 kDa) with following characteristics: sedimentation constant--4.9 S; IP--4.8; dissociation constant (Kd) for estradiol-17beta binding--0.7 nmol; binding sites--0.746 pmol/mg protein; relative binding affinity--estradiol-17beta--100, estrone--80 and estriol--30; specificity--does not bind, other natural steroids, synthetic estrogens, antiestrogens and bioflavonoids. Importantly, immunosuppressants, neuroleptic and carcinogens influence 3H-estradiol-17beta binding to pER. Interestingly, pER is a serine phosphatase and this may have relevancy to estrogen action in Alzheimer's disease. The polyclonal anti-pER antibody does not react with estrogen receptors (ER). ER antibody does not react with pER. Remarkably, anti-pER antibody reacts with calcineurin, a brain phosphatase and anti-calcineurin antibody reacts with pER. Immunohistochemical analyses showed that pER is undetectable in reproductive organs (except ovary). It is localized on the plasma or the nuclear membranes in some, in cytoplasm and/or nucleus in other cells of non-reproductive organs (skeletal, neural, vascular, hair and retina), and in tumors (mammary, endometrial and prostate cancers, and prostatic hyperplasia). The information presented justifies the proposition that pER may mediate the estrogenic actions in non-reproductive organs.
Brug 254, AZVU, Amsterdam, The Netherlands. rao@online.nl
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D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000818:Animals; D000918:Antibody Specificity; D014150:Antipsychotic Agents / Q000378:metabolism; D001667:Binding, Competitive; D002147:Calmodulin / Q000378:metabolism; D002645:Chickens; D004958:Estradiol / Q000378:metabolism; D004964:Estriol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D004970:Estrone / Q000378:metabolism; D005260:Female; D005836:Genitalia, Female / Q000737:chemistry / Q000648:ultrastructure; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011467:Prostate / Q000737:chemistry / Q000648:ultrastructure; D051381:Rats; D011960:Receptors, Estrogen / Q000187:drug effects / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D014150:Antipsychotic Agents; D002147:Calmodulin; D004967:Estrogens; D007166:Immunosuppressive Agents; D011960:Receptors, Estrogen; D013439:Sulfhydryl Reagents; D004970:Estrone; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; D010744:Phosphoric Monoester Hydrolases; D004964:Estriol