摘要
Androgens are important for the structural and functional integrity of the testis and the prostate and this may in part be mediated by the aromatisation of testosterone to oestradiol. The aim of the present study was to establish an in vivo model that would allow the identification of genes, the expression of which was regulated acutely by androgen and/or oestrogen in the male reproductive system. In rats in which the Leydig cells were ablated by administration of ethane dimethane sulfonate (EDS) 6 days earlier, testosterone esters (T) were administered from day 0 (To), and additional animals were administered either T, 17β-oestradiol benzoate (EB) or diethylstilbestrol (DES) for 1 or 4 h on day 6 after EDS-treatment. Nuclear immunoexpression of the androgen receptor (AR) was reduced or absent from the testis but unaffected in the ventral prostate following these treatments. ERβ immunoexpression in these tissues was unchanged. Northern blot analysis showed that EB and DES as well as T administration 4 h earlier could modulate mRNA expression of two androgen-responsive genes, C3 and SGP-2, in the prostate. The co-administration of T or EB with the AR antagonist, flutamide, or with the ER antagonist, ICI 182,780 (ICI), did not block the suppression of SGP-2 mRNA expression by T or EB. In contrast, the upregulation of C3 mRNA expression by T was successfully antagonised by both flutamide and by ICI. A preliminary evaluation of the expression of three Sertoli cell and five germ cell mRNAs revealed that their expression was not steroid regulated. Our results support the hypothesis that the action of testosterone in the male reproductive system may in part be mediated by its conversion to oestradiol. This in vivo model should prove of value in future studies to identify androgen and oestrogen regulated genes in the male reproductive system.
摘要译文
雄激素对于睾丸和前列腺的结构和功能完整性是重要的，这可能部分地由睾酮对雌二醇的芳香化介导。本研究的目的是建立一个体内模型，可以识别基因，其雄激素和/或雌激素在雄性生殖系统中表达受急性调节。在通过给予乙烷二甲磺酸盐（EDS）6天之前消除睾丸间质细胞的大鼠中，从第0天（To）开始给予睾酮酯（T）并且在EDS治疗后第6天给予额外的动物T或17β-雌二醇苯甲酸酯（EB）或己烯雌酚（DES）1或4小时。在这些治疗之后，雄激素受体（AR）的核免疫表达在睾丸中减少或消失，但在腹侧前列腺中不受影响。ERβ免疫表达在这些组织中没有变化。Northern印迹分析表明，EB和DES以及4小时前的T可以调节前列腺中两种雄激素应答基因C3和SGP-2的mRNA表达。T或EB与AR拮抗剂氟他胺或ER拮抗剂ICI 182,780（ICI）联合给药不能阻断T或EB对SGP-2 mRNA表达的抑制。相反，T的C3 mRNA表达上调被氟他胺和ICI成功拮抗。对三种支持细胞和五种生殖细胞mRNA表达的初步评估显示它们的表达不是类固醇调节的。我们的研究结果支持睾酮在男性生殖系统中的作用部分可以通过其转化为雌二醇而介导的假设。这种体内模型应该在未来的研究中证明雄激素和雌激素调节基因在男性生殖系统中的价值。
Katie JTurner;MichelleMorley;SheilaMacPherson;Michael RMillar;Julie AWilson;Richard MSharpe;Philippa T.KSaunders;. Modulation of gene expression by androgen and oestrogens in the testis and prostate of the adult rat following androgen withdrawal[J]. Molecular and Cellular Endocrinology, 2001,178(1-2): 73-87