Intratesticular Testosterone and Spermatogenesis in Man

描述(由申请人提供)：对大鼠和人来说，睾丸中的总睾酮浓度远远高于血清中的浓度，这一点得到了很好的证实。我们知道，在不影响精子发生的情况下，睾丸内的睾酮可以减少50%-60%，但所需的睾酮浓度仍然是血清睾酮浓度的10倍。这类信息如果对人类可用，对于理解和治疗至少一部分男性不孕症可能被证明是非常有价值的。不幸的是，我们对人类睾丸内睾丸液中雄激素的含量以及睾丸内雄激素与人类精子发生之间的关系知之甚少。我们最近对人类的研究表明，与大鼠一样，血清和睾丸内的睾酮浓度之间存在梯度；睾丸内的睾酮水平被发现比正常血清睾酮水平高100倍。我们还不知道人类睾丸中需要多少睾丸素来维持或恢复定量的正常精子生成，因为到目前为止，与在大鼠身上进行的实验研究对人类来说是不可行的。此外，我们对任何哺乳动物睾丸中生物可用雄激素的浓度知之甚少，因此几乎对生物可用雄激素浓度与大鼠或人类精子发生之间的关系一无所知。 该项目的主要目标是确定和量化人类睾丸中的雄激素含量，评估睾丸内雄激素的生物利用度，通过实验确定睾丸内生物可用雄激素浓度与精子发生的关系，并检测睾酮替代方式对睾丸内生物可用雄激素浓度的影响以及对不育男性精子发生的影响。

DESCRIPTION (provided by applicant): It is well established for both rat and man that the total testosterone concentration within the testes is far higher than that in serum. We know for the that intratesticular testosterone can be reduced by 50-60% without effect on spermatogenesis, but that the required 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 at least subsets of men with infertility. Unfortunately, we know little about the androgen content of intratesticular fluid within the human testis or the relationship between intratesticular androgens and human spermatogenesis. 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 normal serum testosterone levels. We do not yet know how much of the testosterone within the human testis is required either to maintain or restore quantitatively normal spermatogenesis because, as yet, experimental studies comparable to those performed in the rat have not been feasible for the human. Moreover, we know little about the concentration of bioavailable androgens within the testes of any mammal, and therefore virtually nothing about the relationship between bioavailable androgen concentration and spermatogenesis in rat or man. The major objectives of this project are to identify and quantify the androgen content of the human testis, to assess the bioavailability of intratesticular androgens, to experimentally determine the relationship between bioavailable intratesticular androgen concentration and spermatogenesis, and to examine the effect of testosterone replacement modalities on intratesticular bioavailable androgen concentration and on spermatogenesis in subfertile men.