{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/71452"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/71452","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Analysis of Estrogen and Antiestrogen Receptor Complexes","abstract":"I have used affinity labeling ligands for the estrogen receptor (ER) to examine the structure and relatedness of ER in different target tissues and species. In addition, I have characterized the first efficient and selective affinity labeling estrogen, ketononestrol aziridine (KNA).","abstract_html":"I have used affinity labeling ligands for the estrogen receptor (ER) to examine the structure and relatedness of ER in different target tissues and species. In addition, I have characterized the first efficient and selective affinity labeling estrogen, ketononestrol aziridine (KNA).","abstract_has_math":false,"creators":["Elliston, Jonathan Franklin"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Physiology","degree_department":null,"school":null,"contributors":["Katzenellenbogen, Benita S."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-12-16T06:45:53Z","date_published":"2014-12-16T06:45:53Z","updated_at":"2026-07-22T22:26:04Z","subjects":["Biology, Animal Physiology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["(UMI)AAI8803030"],"render_values":[{"text":"(UMI)AAI8803030","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/71452","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Katzenellenbogen, Benita S."]},{"key":"dc:creator","label":"Author","values":["Elliston, Jonathan Franklin"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2014-12-16T06:45:53Z","10000-01-01","1987"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Physiology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology, Animal Physiology"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/71452","(UMI)AAI8803030"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["I have used affinity labeling ligands for the estrogen receptor (ER) to examine the structure and relatedness of ER in different target tissues and species. In addition, I have characterized the first efficient and selective affinity labeling estrogen, ketononestrol aziridine (KNA).","KNA has an apparent relative binding affinity of 8% that of estradiol and shows time-dependent irreversible binding to the ER. The agonistic activity of KNA is evident in MCF-7 cells in culture, where it increases cell growth rate and elevates the level of progesterone receptor. Labeling with ($\\sp3$H) KNA proceeds in a time-, concentration-, and temperature-dependent manner; labeling is efficient and selective and, by competition studies, was shown to be estrogen specific. ER covalently labeled with ($\\sp3$H) KNA sediments as a 4S species on high salt sucrose gradients, and its sedimentation position is shifted by treatment with monoclonal antibodies. On SDS-polyacrylamide gels, the labeled species migrates with a molecular weight (M$\\sb{\\rm r}$) of 66,000 daltons.","ER covalently labeled with the estrogen affinity label ($\\sp3$H) ketononestrol aziridine (KNA) or with the antiestrogen affinity label ($\\sp3$H) tamoxifen aziridine (TAZ) was subjected to limited proteolysis with trypsin (T), chymotrypsin (C), and V8 protease (V8) and analyzed on SDS-polyacrylamide gels. The similar M$\\sb{\\rm r}$ of intact receptors (66,000 daltons) and the proteolytic digest patterns indicate extensive homology among ER from breast (human), pituitary (rat) and uterus (rat) when liganded with estrogen or antiestrogen.","Each protease generated a distinctive ladder of ER fragments and the patterns were virtually identical for ER labeled with KNA or TAZ. Each protease yielded a relatively "resistant" receptor fragment of ca. 28,000-35,000 daltons. T and C at higher concentrations generated a smaller 6,000-8,000 dalton digest product that still contained the ($\\sp3$H) KNA- or ($\\sp3$H) TAZ-labeled binding site, indicating that the steroid-binding domain is restricted to a relatively small segment of the receptor and is similar for ER from these 3 different target cells.","Made available in DSpace on 2014-12-16T06:45:53Z (GMT). No. of bitstreams: 1 8803030.pdf: 3064378 bytes, checksum: 85c819216e19a1e759f32ec0e10bbbe8 (MD5) Previous issue date: 1987","Embargo set by: Seth Robbins for item 71618 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","98 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1987."]},{"key":"dc:title","label":"Title","values":["Analysis of Estrogen and Antiestrogen Receptor Complexes"]}]}],"canonical_facts":{"dc:contributor":["Katzenellenbogen, Benita S."],"dc:creator":["Elliston, Jonathan Franklin"],"dc:date":["2014-12-16T06:45:53Z","10000-01-01","1987"],"dc:description":["I have used affinity labeling ligands for the estrogen receptor (ER) to examine the structure and relatedness of ER in different target tissues and species. In addition, I have characterized the first efficient and selective affinity labeling estrogen, ketononestrol aziridine (KNA).","KNA has an apparent relative binding affinity of 8% that of estradiol and shows time-dependent irreversible binding to the ER. The agonistic activity of KNA is evident in MCF-7 cells in culture, where it increases cell growth rate and elevates the level of progesterone receptor. Labeling with ($\\sp3$H) KNA proceeds in a time-, concentration-, and temperature-dependent manner; labeling is efficient and selective and, by competition studies, was shown to be estrogen specific. ER covalently labeled with ($\\sp3$H) KNA sediments as a 4S species on high salt sucrose gradients, and its sedimentation position is shifted by treatment with monoclonal antibodies. On SDS-polyacrylamide gels, the labeled species migrates with a molecular weight (M$\\sb{\\rm r}$) of 66,000 daltons.","ER covalently labeled with the estrogen affinity label ($\\sp3$H) ketononestrol aziridine (KNA) or with the antiestrogen affinity label ($\\sp3$H) tamoxifen aziridine (TAZ) was subjected to limited proteolysis with trypsin (T), chymotrypsin (C), and V8 protease (V8) and analyzed on SDS-polyacrylamide gels. The similar M$\\sb{\\rm r}$ of intact receptors (66,000 daltons) and the proteolytic digest patterns indicate extensive homology among ER from breast (human), pituitary (rat) and uterus (rat) when liganded with estrogen or antiestrogen.","Each protease generated a distinctive ladder of ER fragments and the patterns were virtually identical for ER labeled with KNA or TAZ. Each protease yielded a relatively "resistant" receptor fragment of ca. 28,000-35,000 daltons. T and C at higher concentrations generated a smaller 6,000-8,000 dalton digest product that still contained the ($\\sp3$H) KNA- or ($\\sp3$H) TAZ-labeled binding site, indicating that the steroid-binding domain is restricted to a relatively small segment of the receptor and is similar for ER from these 3 different target cells.","Made available in DSpace on 2014-12-16T06:45:53Z (GMT). No. of bitstreams: 1 8803030.pdf: 3064378 bytes, checksum: 85c819216e19a1e759f32ec0e10bbbe8 (MD5) Previous issue date: 1987","Embargo set by: Seth Robbins for item 71618 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","98 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1987."],"dc:identifier":["http://hdl.handle.net/2142/71452","(UMI)AAI8803030"],"dc:subject":["Biology, Animal Physiology"],"dc:title":["Analysis of Estrogen and Antiestrogen Receptor Complexes"],"dc:type":["text"],"thesis:degree_discipline":["Physiology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:26:04Z"}