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 0.5-50μM morphine for 3h in vitro. Morphine at ≥0.5μM significantly reduced total androgen secretion. Morphine at 50μM also compromised luteinizing hormone (LH, 10mg/kg), 8Br-cAMP (1mM), and 22R-hydroxycholesterol (20μM) 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 ≥0.5μM downregulated Star expression and at ≥5μM downregulated Cyp11a1 expression. Morphine also significantly reduced STAR (≥0.5μM) and reduced CYP11A1 (≥5μM) levels. 0.5μM 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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