Morphine compromises androgen biosynthesis by immature Leydig cells from pubertal rat testes in vitro.

IF 2.2 4区医学 Q3 TOXICOLOGY

Toxicology Research Pub Date : 2024-01-25 eCollection Date: 2024-02-01 DOI:10.1093/toxres/tfae001

Yao Lv, Yaoyao Dong, Ming Su, Hang Lin, Qiqi Zhu, Huitao Li

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Abstract

Morphine is an analgesic in the opiate family, isolated from many plants. It can inhibit androgen biosynthesis by Leydig cells. Whether morphine directly inhibits androgen biosynthesis and underlying mechanism remains unclear. To investigate the influence of morphine on androgen secretion by rat immature Leydig cells (ILCs) and possible mechanism. Rat ILCs were treated with 0.5-50 μM morphine for 3 h in vitro. Morphine at ≥0.5 μM significantly reduced total androgen secretion. Morphine at 50 μM also compromised luteinizing hormone (LH, 10 mg/kg), 8Br-cAMP (1 mM), and 22R-hydroxycholesterol (20 μM) stimulated total androgen, androstanediol, and testosterone secretion, without affecting pregnenolone, progesterone, androstenedione mediated androgen secretion and testosterone and dihydrotestosterone mediated androstanediol secretion. Further analysis revealed that morphine at ≥0.5 μM downregulated Star expression and at ≥5 μM downregulated Cyp11a1 expression. Morphine also significantly reduced STAR (≥0.5 μM) and reduced CYP11A1 (≥5 μM) levels. 0.5 μM naloxone significantly antagonized morphine-mediated action. In conclusion, morphine might cause side effects by suppressing androgen biosynthesis via u opioid receptor.

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吗啡会影响青春期大鼠睾丸未成熟莱蒂格细胞在体外的雄激素生物合成。

吗啡是从许多植物中分离出来的阿片类镇痛药。它可抑制莱德细胞的雄激素生物合成。吗啡是否直接抑制雄激素的生物合成及其机制尚不清楚。为了研究吗啡对大鼠未成熟莱德细胞（ILCs）分泌雄激素的影响及可能的机制。在体外用 0.5-50 μM 吗啡处理大鼠 ILCs 3 小时。吗啡浓度≥0.5 μM时可明显降低雄激素的总分泌量。50 μM的吗啡也会影响黄体生成素（LH，10 mg/kg）、8Br-cAMP（1 mM）和22R-羟基胆固醇（20 μM）刺激的总雄激素、雄甾二醇和睾酮的分泌，但不影响孕烯醇酮、孕酮和雄烯二酮介导的雄激素分泌以及睾酮和双氢睾酮介导的雄甾二醇分泌。进一步的分析表明，吗啡≥0.5 μM时会下调Star的表达，≥5 μM时会下调Cyp11a1的表达。吗啡还能明显降低 STAR（≥0.5 μM）和 CYP11A1（≥5 μM）的水平。0.5 μM 纳洛酮能明显拮抗吗啡介导的作用。总之，吗啡可能通过u阿片受体抑制雄激素的生物合成而产生副作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology Research TOXICOLOGY-

CiteScore

3.60

自引率

0.00%

发文量

期刊介绍： A multi-disciplinary journal covering the best research in both fundamental and applied aspects of toxicology