title: An endogenous ligand for type II binding sites in normal and neoplastic tissues.
abstract: The rat uterus contains two classes of specific nuclear estrogen binding sites which may be involved in estrogen action. Type I sites represent the classic estrogen receptor (Kd 1 nM) and type II sites (Kd 10-20 nM) are stimulated in the nucleus by estrogen under conditions which cause uterine hyperplasia. Dilution of uterine nuclear fractions from estrogen treated rats prior to quantitation of estrogen binding sites by [3H]-estradiol exchange results in an increase (3-4 fold) in the measurable quantities of the type II site. Estimates of type I sites are not affected by dilution. These increases in type II sites following nuclear dilution occur independently of protein concentration and result from the dilution of a specific endogenous inhibitor of [3H]-estradiol binding to these sites. The inhibitor activity is present in cytosol preparations from rat uterus, spleen, diaphragm, skeletal muscle and serum. Preliminary characterization of the inhibitor activity by Sephadex G-25 chromatography shows two distinct peaks which are similar in molecular weight (300). These components (alpha and beta) can be separated on LH-20 chromatography since the beta-peak component is preferentially retained on this lipophilic resin. Partial purification of the LH-20-beta inhibitor component by high performance liquid chromatography and gas-liquid chromatography-mass spectrometric analysis suggest the putative inhibitor activity is not steroidal in nature and consists of two very similar phenanthrene-like molecules (molecular weights 302 and 304). Analysis of cytosol preparations on LH-20 chromatography shows that non-neoplastic tissues (uterus, liver, lactating mammary gland) contain both alpha and beta inhibitor components whereas estrogen-induced rat mammary tumors contain very low to non-measurable quantities of the beta-peak inhibitor activity.
mesh_terms: D000818:Animals; D001665:Binding Sites; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004958:Estradiol / Q000378:metabolism; D005260:Female; D007774:Lactation; D008099:Liver / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D013058:Mass Spectrometry; D008970:Molecular Weight; D009132:Muscles / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
chemical_list: D011960:Receptors, Estrogen; D004958:Estradiol