雄性F344大鼠自发性Leydig细胞瘤的比较医学研究

Comparative Medicine Study on Male Fishar344 Rats Spontaneous Leydig cell tumor

目的初步探讨雄性F344大鼠自发性Leydig细胞瘤与血清性激素含量及Leydig细胞AR、LH、ER表达之间的关系。方法26月龄雄性F344大鼠5只(L组),4、7、10、13月龄雄性F344、SD、Wistar大鼠各10只(分别记为A1、A2、A3、A4组,B1、B2、B3、B4组,C1、C2、C3、C4组)。各组睾丸组织切片HE染色,L组睾丸组织电镜观察,各组(除L组外)睾丸组织切片Leydig细胞雄激素受体、黄体生成素、雌激素受体免疫组化染色,放射免疫测定各组血清睾酮、黄体生成素、雌二醇、催乳素、卵泡刺激素、孕酮含量。结果1.A3组部分Leydig细胞轻度增生;A4组部分Leydig细胞中度增生,形成增生灶;L组5只大鼠双侧睾丸均发生Leydig细胞瘤。2.A4组Leydig细胞AR表达强于C3组、B4组和C4组(P<0.05)。A3组和A4组Leydig细胞LH表达均强于B3组、B4组、C4组(P<0.05)。A4组Leydig细胞ER表达弱于B1组、B4组、C4组(P<0.05)。3.血清睾酮含量A3组和A4组均显著高于B3、B4、C3、C4组(P<0.01);而L组极低,除了与C4组无统计学差异外,显著低于其它组(P<0.05或P<0.01)。血清LH含量A4组、L组与B4组、C4组之间无统计学差异(P≥0.05)。血清E2含量L组除了与B1、B2组无差异(P≥0.05)外,明显高于其它组(P<0.05或P<0.01)。血清PRL含量L组明显高于A4组(P<0.05),且此二组均显著高于其它组(P<0.05或P<0.01)。血清FSH含量三种品系大鼠相同月龄组之间无统计学差异(P≥0.05),A4组、B4组、C4组、L组基本相同。血清孕酮含量L组成倍高于其它组(P<0.01)。结论雄性F344大鼠Leydig细胞瘤绝大多数为良性,其应该是由Leydig细胞增生并形成增生灶到瘤变逐渐演变而成的。Leydig细胞LH、AR表达较强与大龄雄性F344大鼠Leydig细胞增生并形成增生灶有关。26月龄雄性F344大鼠Leydig细胞瘤可能与其血清T含量极低、血清E2和孕酮含量相对较高有关,而与其血清LH和FSH含量变化关系不紧密;血清PRL含量相对较高应该与其Leydig细胞增生和肿瘤发生过程有关。

Objective To explore the relationship between Leydig cell tumor and levels of sex hormones and the expression levels ofAR, LH and ER in Leydig cells in male Fisher344 rats. Methods Male Fisher344, Sprague Dawleg, Wistar rats were respectively divided into 4-month-old group（group A1, B1, C1, 7-month-old group（group A2, BE, C2）, 10-month-old group （group A3, B3, C3）, 13-month-old group（group A4, B4, C4）. Each group comprised of ten rats. In addition, another group was five 26- month-old male Fisher344 rats （group L）. Pathologic changes in testes were observed with microscope. Testes of group L were observed with transmission electron microscope. Immuno-histochemistry analysis of androgen receptor, luteinizing hormone, estrogen receptor were taken in tests by SABC method, in every group except group L. The levels of testosterone （T）, luteinizing hormone （LH）, estradiol （E2）, prolactin （PRL）, follicle-stimulating hormone （FSH） and progesterone （P） in sera of each group were measured with radioimmunological analysis method. Results Hyperplasia of Leydig cell occurred in group A3, and more hyperplasia in group A4, and focal hyperplasia had formatted in some cases. All testes of group L had generated Leydig cell tumor. The expression level of AR in Leydig cells in group A4 was higher than that of group C3, B4, C4 （P〈0.05）. The expression levels of LH in Leydig cell in group A3 and A4 were more than that of group B3, B4 and C4 （P〈0.05）. The expression level of ER in Leydig cell in 1 group A4 was less than that of group B1, B4 and C4（P〈0.05）.The level of sera T of group A3 or A4 was higher than that of group B3, B4, C3 or C4（P〈0.01）. Group L has the lowest level of sera T and it was lower than that of the other groups（P〈0.05 or P〈0.01） except group C4（P ≥ 0.05）. There were no significant differences between level of sera LH group L and that of group A4, B4, C4（≥0.05）.The level of sera E2 of group L was the highest, which was significantly higher than that of the other groups （P〈0.05） except group B1 and BE（P ≥ 0.05）. The level of sera PRL of group L was significantly higher than that of group A4（P〈0.05）, and one of both groups was respectively higher than other groups（P〈0.01）. There is no significant difference of the level of sera FSH of the same age groups （P ≥ 0.05）, and the levels of sera FSH of group L, A4, B4 and C4 were almost the same. The level of sera P of group L was significantly higher than that of the other groups（P〈0.01）. Conclusions Most of the Leydig cell tumors in male Fisher344 rats were benign tumor. Leydig cell tumor in male Fisher344 rats may be developed from hyperplasia and focal hyperplasia of Leydig cell. There was a significant correlation between the relatively more expression level of LH and AR in Leydig cell and hyperplasia and focal hyperplasia of Leydig cell in male Fisher344 rats. The development of spontaneous Leydig cell tumors in old male Fisher344 rats may be related to their extremely low level of sera T and the relatively low level sera E2 and P but uncorrelated with the level of sera FSH and LH. The relatively high level ofsera PRL may be related to Leydig cell hyperplasia and tumor generation.