Seidlová-Wuttke D, Prelle K, Fritzemeier K-H, Wuttke Wolfgang
Department of Clinical and Experimental Endocrinology, University of Goettingen, Germany.
Bone. 2008 Nov;43(5):849-55. doi: 10.1016/j.bone.2008.07.237. Epub 2008 Jul 29.
The functions of estrogen receptors (ER) alpha and beta (ER-alpha and beta) in bone and fat tissue are not precisely described. Therefore we studied the effects of a specific ERalpha and ERbeta agonist in bone and fat of ovariectomized (ovx) rats and compared them with the effects of estradiol (E2). Animals were s.c. injected for 4-weeks with 3 doses of the ERalpha agonist 16alpha-LE2 or the ERbeta agonist 8beta-VE2 or with E2. The intermediate doses were antagonized by an additional daily treatment with ICI (1.53mg). Bone and fat parameters were evaluated by quantitative computer tomography (qCT). Estrogen regulated hormones were also measured. Uterine weights were stimulated; serum LH and leptin levels suppressed E2 and the ERalpha agonist. Density of the cancellous metaphyseal structures of the tibia was reduced in the controls which was prevented by E2 and the ERalpha agonist. Endosteal surface, endosteal, periosteal circumferences and fat depots were largest in the controls and the ERbeta treated animals and lowest in the E2 and the 16alpha-LE2 injected ovx rats. Osteocalcin and the CrossLaps were highest in the ovx controls and reduced by E2 and the ERalpha agonist. Serum osteocalcin was stimulated by the ERbeta agonist. The strain strength index (SSI) in relation to the bodyweight - an indicator of bone elasticity - was lowest in controls and increased dose dependently in the E2 and in the ERalpha treated animals. Most effects in the uterus, serum and bone were antagonized by ICI. Most effects in the bone and fat were exerted by mechanisms involving the ERalpha but the ERbeta agonist appears to stimulate osteoblasts.
雌激素受体（ER）α和β（ER-α和ER-β）在骨骼和脂肪组织中的功能尚未得到精确描述。因此，我们研究了一种特异性ERα和ERβ激动剂对去卵巢（ovx）大鼠骨骼和脂肪的影响，并将其与雌二醇（E2）的作用进行比较。动物皮下注射3种剂量的ERα激动剂16α-LE2或ERβ激动剂8β-VE2或E2，持续4周。中间剂量通过每天额外注射ICI（1.53mg）进行拮抗。通过定量计算机断层扫描（qCT）评估骨骼和脂肪参数。还测量了雌激素调节的激素。子宫重量增加；血清促黄体生成素（LH）和瘦素水平受到E2和ERα激动剂的抑制。对照组胫骨干骺端松质结构密度降低，E2和ERα激动剂可预防这种情况。骨内膜表面、骨内膜、骨膜周长和脂肪库在对照组和接受ERβ治疗的动物中最大，在注射E2和16α-LE2的ovx大鼠中最低。骨钙素和CrossLaps在ovx对照组中最高，E2和ERα激动剂可使其降低。血清骨钙素受到ERβ激动剂的刺激。与体重相关的应变强度指数（SSI）——骨骼弹性的指标——在对照组中最低，在接受E2和ERα治疗的动物中呈剂量依赖性增加。ICI可拮抗子宫、血清和骨骼中的大多数作用。骨骼和脂肪中的大多数作用是通过涉及ERα的机制发挥的，但ERβ激动剂似乎可刺激成骨细胞。
