Intratesticular Testosterone and Spermatogenesis in Man

描述（由申请方提供）：大鼠和人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。我们知道睾丸内睾酮可以减少50-60%而不影响精子发生，但所需的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至少部分男性不育症。不幸的是，我们对人类睾丸内睾丸液的雄激素含量或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，血清中睾酮浓度与睾丸内睾酮浓度之间存在梯度;睾丸内睾酮水平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酮来维持或恢复正常的精子发生，因为到目前为止，与在大鼠中进行的实验研究相比，在人类中还不可行。此外，我们对任何哺乳动物睾丸内生物可利用雄激素的浓度知之甚少，因此对大鼠或人的生物可利用雄激素浓度与精子发生之间的关系几乎一无所知。 该项目的主要目标是确定和量化人类睾丸的雄激素含量，评估睾丸内雄激素的生物利用度，通过实验确定生物可利用的睾丸内雄激素浓度和精子发生之间的关系，并检查睾丸激素替代方式对睾丸内生物可利用的雄激素浓度和低生育力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.