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姜黄素对睾丸间质细胞功能的影响及潜在治疗用途。

Curcumin effects on Leydig cell functions and potential therapeutic uses.

作者信息

Raices Trinidad, Luisa Varela María, Abiuso Adriana María Belén, Pereyra Elba N, Mondillo Carolina, Pignataro Omar P, Riera María Fernanda

机构信息

Laboratory of Molecular Endocrinology and Signal Transduction, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina.

Centro de Investigaciones Endocrinológicas 'Dr. César Bergadá' (CEDIE-CONICET-FEI), División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.

出版信息

Endocr Oncol. 2023 Feb 1;3(1):e220075. doi: 10.1530/EO-22-0075. eCollection 2023 Jan 1.

Abstract

Curcumin has been ascribed with countless therapeutic effects, but its impact on testicular function has been scarcely researched. Leydig cells comprise the androgen-secreting population of the testis and may give rise to Leydig cell tumours (LCTs). Due to their steroid-secreting nature, LCTs entail endocrine, reproductive, and psychological disorders. Approximately 10% are malignant and do not respond to chemotherapy and radiotherapy. The aim of this study was to assess curcumin's impact on Leydig cells' functions and its potential effect on LCT growth. assays on MA-10 Leydig cells showed that curcumin (20-80 µmol/L) stimulates acute steroidogenesis, both in the presence and absence of db-cAMP. This effect is accompanied by an increase in StAR expression. Regarding curcumin's cytostatic capacity, we show that 40-80 µmol/L curcumin reduces MA-10 Leydig cells' proliferative capacity, which could be explained by the arrest in G2/M and the reduced viability due to the activation of the apoptotic pathway. Finally, CB6F1 mice were inoculated with MA-10 cells to generate ectopic LCT in both flanks. They received i.p. injections of 20 mg/kg curcumin or vehicle every other day for 15 days. We unveiled curcumin's capacity to inhibit LCT growth as evidenced by reduced tumour volume, weight, and area under the growth curves. No detrimental effects on general health parameters or testicular integrity were observed. These results provide novel evidence of curcumin's effects on the endocrine cell population of the testis and propose this natural compound as a therapeutic agent for LCT.

摘要

姜黄素具有无数的治疗作用,但其对睾丸功能的影响却鲜有研究。睾丸间质细胞是睾丸中分泌雄激素的细胞群,可能会引发睾丸间质细胞瘤(LCTs)。由于其分泌类固醇的特性,LCTs会导致内分泌、生殖和心理紊乱。大约10%是恶性的,对化疗和放疗无反应。本研究的目的是评估姜黄素对睾丸间质细胞功能的影响及其对LCT生长的潜在作用。对MA-10睾丸间质细胞的检测表明,姜黄素(20-80µmol/L)在有和没有db-cAMP的情况下均能刺激急性类固醇生成。这种作用伴随着类固醇生成急性调节蛋白(StAR)表达的增加。关于姜黄素的细胞生长抑制能力,我们发现40-80µmol/L的姜黄素会降低MA-10睾丸间质细胞的增殖能力,这可能是由于细胞周期停滞在G2/M期以及凋亡途径激活导致活力降低所致。最后,将CB6F1小鼠接种MA-10细胞,在双侧胁腹生成异位LCT。它们每隔一天接受腹腔注射20mg/kg姜黄素或赋形剂,持续15天。我们发现姜黄素具有抑制LCT生长的能力,肿瘤体积、重量和生长曲线下面积减小证明了这一点。未观察到对一般健康参数或睾丸完整性的有害影响。这些结果为姜黄素对睾丸内分泌细胞群的作用提供了新的证据,并提出这种天然化合物可作为LCT的治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bf3/10305475/f6d7eee6172b/EO-22-0075fig1.jpg

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