Hedger M P, Khatab S, Gonzales G, de Kretser D M
Institute of Reproduction and Development, Monash University, Monash Medical Centre, Clayton, Vic., Australia.
Reprod Fertil Dev. 1995;7(5):1101-9. doi: 10.1071/rd9951101.
In this study, adult male rats were injected intraperitoneally with a single dose of serotonin (5-hydroxytryptamine, 5HT; 10 mg kg-1 bodyweight) for 2 h or 18 h, or daily with graded doses of 5HT (0.1-10 mg kg-1) for four days before being killed. Serum and testicular interstitial fluid (IF) concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and immunoreactive-inhibin were measured by radioimmunoassay, and one testis was removed for histological examination. At 2 h after a single injection, 5HT caused a significant inhibition of serum concentrations of LH and inhibin, recovered IF volume and intratesticular testosterone concentrations; testis weight and serum concentrations of testosterone and FSH were unaffected. At 18 h after injection, all parameters had returned to normal, with the exception of intratesticular testosterone concentration which remained lower than normal. The lowest 5HT dose (0.1 mg kg-1) had no effect on any parameter following four daily injections. At a dose of 1.0 mg kg-1 5HT, there was a four-fold increase in the concentration of serum LH, but testis weight, recovered IF volume, testosterone and inhibin concentrations and serum concentrations of FSH were not significantly affected. At the highest dose of 5HT (10 mg kg-1) after four daily injections, testis weight decreased, and IF volume increased nearly three-fold. Testis concentrations of inhibin and serum testosterone were reduced, whereas serum concentrations of both LH and FSH were elevated; intratesticular testosterone concentrations did not differ from controls. Only at the highest dose of 5HT was disruption to the seminiferous epithelium observed, with focal damage ranging in severity from increased degeneration of spermatogenic cell profiles, to complete loss of the germinal epithelium; however, many tubule profiles displayed completely normal spermatogenesis. The acute IF volume reduction and spermatogenic disruption in 5HT-treated rats were consistent with localized ischaemia due to constriction of the testicular arterial supply. The eventual increase in IF volume observed after 5HT treatment appeared to be secondary to the loss of germ cells. Although 5HT also inhibited pituitary LH release and Leydig cell steroidogenesis, these effects appeared to play only a minor role in the induction of spermatogenic damage.
在本研究中,成年雄性大鼠腹腔注射单剂量血清素(5-羟色胺,5HT;10毫克/千克体重),持续2小时或18小时,或在处死前连续四天每天注射不同剂量的5HT(0.1 - 10毫克/千克)。采用放射免疫分析法测定血清和睾丸间质液(IF)中促黄体生成素(LH)、促卵泡生成素(FSH)、睾酮和免疫反应性抑制素的浓度,并摘除一侧睾丸进行组织学检查。单次注射后2小时,5HT显著抑制血清中LH和抑制素的浓度,使IF体积恢复,睾丸内睾酮浓度恢复;睾丸重量以及血清中睾酮和FSH的浓度未受影响。注射后18小时,除睾丸内睾酮浓度仍低于正常外,所有参数均恢复正常。连续四天每天注射最低剂量的5HT(0.1毫克/千克)对任何参数均无影响。5HT剂量为1.0毫克/千克时,血清LH浓度增加了四倍,但睾丸重量、恢复的IF体积、睾酮和抑制素浓度以及血清FSH浓度均未受到显著影响。连续四天每天注射最高剂量的5HT(10毫克/千克)后,睾丸重量减轻,IF体积增加近三倍。睾丸中抑制素浓度和血清睾酮浓度降低,而血清中LH和FSH浓度均升高;睾丸内睾酮浓度与对照组无差异。仅在最高剂量的5HT时观察到生精上皮受到破坏,局部损伤严重程度从生精细胞形态的变性增加到生精上皮完全丧失不等;然而,许多小管形态显示生精过程完全正常。5HT处理的大鼠中急性IF体积减少和生精破坏与睾丸动脉供应收缩导致的局部缺血一致。5HT处理后最终观察到的IF体积增加似乎是生殖细胞丢失的继发结果。尽管5HT也抑制垂体LH释放和睾丸间质细胞类固醇生成,但这些作用在生精损伤诱导中似乎仅起次要作用。