{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:51:43Z","timestamp":1792543903745,"version":"4.5.0"},"reference-count":47,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,10,1]]},"abstract":"<jats:p>The discovery of a second estrogen receptor (ER), called ER\u03b2, in 1996 sparked intense interest within the scientific community to discover its role in mediating estrogen action. However, despite more than 6 yr of research into the function of this receptor, its physiological role in mediating estrogen action remains unclear and controversial. We have developed a series of highly selective agonists for ER\u03b2 and have characterized their activity in several clinically relevant rodent models of human disease. The activity of one such compound, ERB-041, is reported here. We conclude from these studies that ER\u03b2 does not mediate the bone-sparing activity of estrogen on the rat skeleton and that it does not affect ovulation or ovariectomy-induced weight gain. In addition, these compounds are nonuterotrophic and nonmammotrophic. However, ERB-041 has a dramatic beneficial effect in the HLA-B27 transgenic rat model of inflammatory bowel disease and the Lewis rat adjuvant-induced arthritis model. Daily oral doses as low as 1 mg\/kg reverse the chronic diarrhea of HLA-B27 transgenic rats and dramatically improve histological disease scores in the colon. The same dosing regimen in the therapeutic adjuvant-induced arthritis model reduces joint scores from 12 (maximal inflammation) to 1 over a period of 10 d. Synovitis and Mankin (articular cartilage) histological scores are also significantly lowered (50\u201375%). These data suggest that one function of ER\u03b2 may be to modulate the immune response, and that ER\u03b2-selective ligands may be therapeutically useful agents to treat chronic intestinal and joint inflammation.<\/jats:p>","DOI":"10.1210\/en.2003-0550","type":"journal-article","created":{"date-parts":[[2003,9,19]],"date-time":"2003-09-19T22:39:04Z","timestamp":1064011144000},"page":"4241-4249","source":"Crossref","is-referenced-by-count":265,"title":["Evaluation of an Estrogen Receptor-\u03b2 Agonist in Animal Models of Human Disease"],"prefix":"10.1210","volume":"144","author":[{"given":"Heather A.","family":"Harris","sequence":"first","affiliation":[{"name":"Women\u2019s Health Research Institute (H.A.H., Y.P.K., J.M., B.S.K., R.C.W., D.E.F., R.A.H., Y.Z.) 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