Department of Trauma Surgery, Orthopaedics and Plastic Surgery, University of Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
Department of Trauma Surgery, Hannover Medical School, University of Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
J Endocrinol Invest. 2024 Mar;47(3):709-720. doi: 10.1007/s40618-023-02188-z. Epub 2023 Sep 6.
Selective androgen (ostarine, OST) and estrogen (raloxifene, RAL) receptor modulators with improved tissue selectivity have been developed as alternatives to hormone replacement therapy. We investigated the combined effects of OST and RAL on muscle tissue in an estrogen-deficient rat model of postmenopausal conditions.
Three-month-old Sprague Dawley rats were divided into groups: (1) untreated non-ovariectomized rats (Non-OVX), (2) untreated ovariectomized rats (OVX), (3) OVX rats treated with OST, (4) OVX rats treated with RAL, (5) OVX rats treated with OST and RAL. Both compounds were administered in the diet. The average dose received was 0.6 ± 0.1 mg for OST and 11.1 ± 1.2 mg for RAL per kg body weight/day. After thirteen weeks, rat activity, muscle weight, structure, gene expression, and serum markers were analyzed.
OST increased muscle weight, capillary ratio, insulin-like growth factor 1 (Igf-1) expression, serum phosphorus, uterine weight. RAL decreased muscle weight, capillary ratio, food intake, serum calcium and increased Igf-1 and Myostatin expression, serum follicle stimulating hormone (FSH). OST + RAL increased muscle nucleus ratio, uterine weight, serum phosphorus, FSH and luteinizing hormone and decreased body and muscle weight, serum calcium. Neither treatment changed muscle fiber size. OVX increased body and muscle weight, decreased uterine weight, serum calcium and magnesium.
OST had beneficial effects on muscle in OVX rats. Side effects of OST on the uterus and serum electrolytes should be considered before using it for therapeutic purposes. RAL and RAL + OST had less effect on muscle and showed endocrinological side effects on pituitary-gonadal axis.
已开发出具有改善组织选择性的选择性雄激素（Ostarine，OST）和雌激素（雷洛昔芬，RAL）受体调节剂，以替代激素替代疗法。我们研究了 OST 和 RAL 对去卵巢绝经后大鼠模型中肌肉组织的联合作用。
将 3 月龄 Sprague Dawley 大鼠分为以下几组：（1）未处理的非卵巢切除大鼠（Non-OVX），（2）未处理的卵巢切除大鼠（OVX），（3）用 OST 处理的 OVX 大鼠，（4）用 RAL 处理的 OVX 大鼠，（5）用 OST 和 RAL 处理的 OVX 大鼠。两种化合物均在饮食中给药。每天每公斤体重分别接受 OST 0.6±0.1mg 和 RAL 11.1±1.2mg 的平均剂量。十三周后，分析大鼠的活动、肌肉重量、结构、基因表达和血清标志物。
OST 增加了肌肉重量、毛细血管比、胰岛素样生长因子 1（IGF-1）表达、血清磷、子宫重量。RAL 降低了肌肉重量、毛细血管比、食物摄入量、血清钙，增加了 IGF-1 和肌肉生长抑制素（Myostatin）的表达、血清卵泡刺激素（FSH）。OST+RAL 增加了肌肉核比、子宫重量、血清磷、FSH 和黄体生成素，减少了体重和肌肉重量、血清钙。两种治疗均未改变肌肉纤维大小。OVX 增加了体重和肌肉重量，降低了子宫重量、血清钙和镁。
OST 对 OVX 大鼠的肌肉有有益的影响。在将 OST 用于治疗目的之前，应考虑其对子宫和血清电解质的副作用。RAL 和 RAL+OST 对肌肉的作用较小，并对垂体-性腺轴产生内分泌副作用。
