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选择性雄激素和雌激素受体调节剂在去势大鼠中的联合应用。

Combination of selective androgen and estrogen receptor modulators in orchiectomized rats.

机构信息

Department of Trauma Surgery, Orthopaedics and Plastic Surgery, University of Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.

Kogod Center On Aging and Division of Endocrinology, Mayo Clinic, Rochester, MN, 55905, USA.

出版信息

J Endocrinol Invest. 2022 Aug;45(8):1555-1568. doi: 10.1007/s40618-022-01794-7. Epub 2022 Apr 16.

Abstract

PURPOSE

Selective androgen and estrogen receptor modulators, ostarine (OST) and raloxifen (RAL), reportedly improve muscle tissue and offer therapeutic approaches to muscle maintenance in the elderly. The present study evaluated the effects of OST and RAL and their combination on musculoskeletal tissue in orchiectomized rats.

METHODS

Eight-month-old Sprague Dawley rats were analyzed. Experiment I: (1) Untreated non-orchiectomized rats (Non-ORX), (2) untreated orchiectomized rats (ORX), (3) ORX rats treated with OST during weeks 0-18 (OST-P), (4) ORX rats treated with OST during weeks 12-18 (OST-T). Experiment II: 1) Non-ORX, (2) ORX, 3) OST-P, (4) ORX rats treated with RAL, during weeks 0-18 (RAL-P), 5) ORX rats treated with OST + RAL, weeks 0-18 (OST + RAL-P). The average daily doses of OST and RAL were 0.4 and 7 mg/kg body weight (BW). Weight, fiber size, and capillarization of muscles, gene expression, serum markers and the lumbar vertebral body were analyzed.

RESULTS

OST-P exerted favorable effects on muscle weight, expression of myostatin and insulin growth factor-1, but increased prostate weight. OST-T partially improved muscle parameters, showing less effect on the prostate. RAL-P did not show anabolic effects on muscles but improved body constitution by reducing abdominal area, food intake, and BW. OST + RAL-P had an anabolic impact on muscle, reduced androgenic effect on the prostate, and normalized food intake. OST and RAL improved osteoporotic bone.

CONCLUSIONS

The OST + RAL treatment appeared to be a promising option in the treatment of androgen-deficient conditions and showed fewer side effects than the respective single treatments.

摘要

目的

选择性雄激素和雌激素受体调节剂,包括 ostarine(OST)和 raloxifen(RAL),据称可改善肌肉组织,并为老年人提供肌肉维持的治疗方法。本研究评估了 OST 和 RAL 及其组合对去势大鼠骨骼肌肉组织的影响。

方法

分析了 8 月龄的 Sprague Dawley 大鼠。实验 I:(1)未处理的非去势大鼠(Non-ORX),(2)未处理的去势大鼠(ORX),(3)在第 0-18 周用 OST 治疗的 ORX 大鼠(OST-P),(4)在第 12-18 周用 OST 治疗的 ORX 大鼠(OST-T)。实验 II:(1)Non-ORX,(2)ORX,(3)OST-P,(4)在第 0-18 周用 RAL 治疗的 ORX 大鼠(RAL-P),(5)在第 0-18 周用 OST+RAL 治疗的 ORX 大鼠(OST+RAL-P)。OST 和 RAL 的平均日剂量分别为 0.4 和 7mg/kg 体重(BW)。分析了肌肉的重量、纤维大小和毛细血管化、基因表达、血清标志物和腰椎椎体。

结果

OST-P 对肌肉重量、肌肉生长抑制素和胰岛素样生长因子-1 的表达有有利影响,但增加了前列腺重量。OST-T 部分改善了肌肉参数,对前列腺的影响较小。RAL-P 对肌肉没有合成代谢作用,但通过减少腹部面积、食物摄入和 BW 改善了体质。OST+RAL-P 对肌肉有合成代谢作用,减少了对前列腺的雄激素作用,并使食物摄入正常化。OST 和 RAL 改善了骨质疏松性骨骼。

结论

OST+RAL 治疗似乎是治疗雄激素缺乏症的一种有前途的选择,其副作用比各自的单一治疗少。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/760c/9270269/e5afc26f9e6b/40618_2022_1794_Fig1_HTML.jpg

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