Erlandsson M C, Jonsson C A, Lindberg M K, Ohlsson C, Carlsten H
Department of Rheumatology and Inflammation Research, University of Göteborg, Sweden.
J Endocrinol. 2002 Nov;175(2):319-27. doi: 10.1677/joe.0.1750319.
Raloxifene is a selective estrogen receptor modulator approved for the prevention of osteoporosis in postmenopausal women. It is selective by having estrogen-agonistic effects on bone, vessels and blood lipids while it is antagonistic on mammary and uterine tissue. Our aim was to study the agonistic and antagonistic properties of the raloxifene analogue LY117018 (LY) on uterus, bone, B lymphopoiesis and B cell function. Oophorectomized and sham-operated animals were treated with s.c. injections of equipotent anti-osteoporotic doses of 17beta-estradiol (E2) (0.1 mg/kg) or LY (3 mg/kg) or vehicle as controls. Effects on bone mineral density (BMD) were studied using peripheral quantitative computed tomography, uterine weight was examined, B lymphopoiesis was examined using flow cytometry and B cell function in bone marrow and spleen was studied by the use of an ELISPOT assay. E2 and LY had similar effects on BMD and bone marrow B lymphopoiesis, while LY had a clear antagonistic effect on endogenous estrogen in uterine tissue and no stimulating effect on the frequency of Ig-producing B cells in sham-operated animals. Our results are discussed in the context of estrogen receptor biology, relations between the immune system and bone metabolism and also with respect to the estrogen-mediated effects on rheumatic diseases.
雷洛昔芬是一种选择性雌激素受体调节剂，已被批准用于预防绝经后妇女的骨质疏松症。它具有选择性，对骨骼、血管和血脂具有雌激素激动作用，而对乳腺和子宫组织具有拮抗作用。我们的目的是研究雷洛昔芬类似物LY117018（LY）对子宫、骨骼、B淋巴细胞生成和B细胞功能的激动和拮抗特性。对去卵巢和假手术的动物皮下注射等效抗骨质疏松剂量的17β-雌二醇（E2）（0.1mg/kg）或LY（3mg/kg）或作为对照的赋形剂进行治疗。使用外周定量计算机断层扫描研究对骨矿物质密度（BMD）的影响，检查子宫重量，使用流式细胞术检查B淋巴细胞生成，并通过ELISPOT测定法研究骨髓和脾脏中的B细胞功能。E2和LY对BMD和骨髓B淋巴细胞生成具有相似的作用，而LY对子宫组织中的内源性雌激素具有明显的拮抗作用，并且对假手术动物中产生Ig的B细胞频率没有刺激作用。我们在雌激素受体生物学、免疫系统与骨代谢之间的关系以及雌激素对风湿性疾病的介导作用的背景下讨论了我们的结果。
