The androgen microenvironment of the human testis and hormonal control of spermatogenesis
The androgen microenvironment of the human testis and hormonal control of spermatogenesis
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DOI：
10.1196/annals.1336.023
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Zirkin, BR
中科院分区：
文献类型：
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作者：
Jarow, JP;Zirkin, BR
对于大鼠和人来说，睾丸内的总睾酮浓度远高于血清中的总睾酮浓度，这一点已得到充分证实。我们知道，大鼠睾丸内睾酮可以减少50-60%，而不会对精子发生产生不良影响，但所需的睾丸内睾酮浓度仍然是血清睾酮浓度的10倍。这种信息，如果可用于人类，可以证明是非常宝贵的理解和治疗选定的男性不育症和男性激素避孕药的发展。遗憾的是，我们对人类睾丸内液中雄激素的含量知之甚少，对睾丸内雄激素与人类精子发生之间的关系也一无所知。使用一种新开发的微创技术重复睾丸采样，我们最近的研究表明，在人类中，在大鼠，血清中的睾酮浓度和睾丸内有一个梯度;睾丸内睾酮水平被发现是100倍高于正常男性的血清睾酮水平。使用液相色谱串联质谱，我们已经表明，睾丸内5 α-二氢睾酮（DHT）水平只有2%的睾酮，因此，尽管更大的亲和力雄激素受体，睾丸内DHT是不显着的正常男性。为了评估人类睾丸中有多少睾酮具有生物活性，我们采用了一种高灵敏度的重组蛋白哺乳动物细胞生物测定法来测量雄激素生物活性。正常人睾丸中的雄激素生物活性大约是放射免疫测定法测量的总睾酮的三分之二，尽管主要雄激素结合蛋白（性激素结合球蛋白和雄激素结合蛋白）的浓度不足以解释这种差异。这一发现表明雄激素可能与人类睾丸中其他未知的分子结合。这与大鼠的精子发生或对激素避孕药反应的人与人之间的差异有何关系，或者是否有关系，目前尚不清楚。我们还不知道人类睾丸内需要多少睾酮来维持或（原文如此）。
It is well established for both rat and man that the total testosterone concentration within the testis is far higher than that in serum. We know for the rat that intratesticular testosterone can be reduced by 50-60% without an adverse effect on spermatogenesis but that the required intratesticular testosterone concentration is still 10-fold greater than serum testosterone concentration. This kind of information, if available for the human, could prove invaluable for understanding and treating select men with infertility and in the development of male hormonal contraceptives. Unfortunately, we know little about the androgen content of intratesticular fluid within the human testis and nothing about the relationship between intratesticular androgens and human spermatogenesis. Using a newly developed minimally invasive technique for repetitive testicular sampling, our recent studies of the human have demonstrated that, as in the rat, there is a gradient between the concentration of testosterone in serum and within the testis; intratesticular testosterone levels were found to be 100-fold higher than serum testosterone levels in normal men. Using liquid chromatography tandem mass spectroscopy, we have shown that intratesticular 5 alpha-dihydrotestosterone (DHT) levels are only 2% that of testosterone and, thus, despite greater affinity for the androgen receptor, intratesticular DHT is not significant in normal men. In order to assess how much of the testosterone within the human testis is bioactive, we adapted a highly sensitive recombinant protein mammalian cell-based bioassay to measure androgen bioactivity. The androgen bioactivity in the normal human testis is roughly two-thirds that of the total testosterone measurable by radioimmunoassay, despite the fact that the concentrations of the major androgen-binding proteins (sex hormone-binding globulin- and androgen-binding protein) are insufficient to account for this difference. This finding suggests that androgens may bind to other, as-yet-unknown molecules in the human testis. How, or if, this relates to spermatogenesis in the rat, or to man-to-man differences in the response to hormonal contraceptives, is not clear. We do not yet know how much testosterone is required within the human testis to either maintain or (sic).