Intratesticular Testosterone and Spermatogenesis in Man

男性睾丸内睾酮和精子发生

• 批准号: 6986830
• 负责人: BARRY R ZIRKIN
• 金额: $ 42.93万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6986830
• 关键词: androgens; blood chemistry; chorionic gonadotropin; clinical research; clomiphene; contraceptives; fertility; fertility promoting drug; fine needle aspiration; hormone regulation /control mechanism; hormone therapy; human subject; human therapy evaluation; laboratory rat; male; patient oriented research; pharmacokinetics; reproductive system disorder chemotherapy; reproductive system pharmacology; semen; sperm analysis; spermatogenesis; spermatogenesis inhibitor; testis; testosterone; androgens; blood chemistry; chorionic gonadotropin; clinical research; clomiphene; contraceptives; fertility; fertility promoting drug; fine needle aspiration; hormone regulation /control mechanism; hormone therapy; human subject; human therapy evaluation; laboratory rat; male; patient oriented research; pharmacokinetics; reproductive system disorder chemotherapy; reproductive system pharmacology; semen; sperm analysis; spermatogenesis; spermatogenesis inhibitor; testis; testosterone

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.

描述（由申请人提供）：大鼠和人都已经确定，睾丸内的总睾丸激素浓度远高于血清中的睾丸激素。我们知道，肠内睾丸激素可以降低50-60％，而不会对精子发生影响，但是所需的睾丸激素浓度仍然比血清睾丸激素浓度大10倍。这种信息（如果适用于人类），对于理解和治疗不育男性的至少子集可能是无价的。不幸的是，我们对人睾丸内中内液的雄激素含量或内部雌激素与人类精子发生之间的关系一无所知。我们对人类的最新研究表明，与大鼠一样，血清中睾丸激素和睾丸内的睾丸激素浓度之间存在梯度。发现肠内睾丸激素水平比正常血清睾丸激素水平高100倍。我们尚不知道人睾丸中需要多少睾丸激素来维持或恢复定量正常的精子发生，因为迄今为止，与大鼠中在大鼠中进行的实验研究对人类尚不可行。此外，我们对在任何哺乳动物的睾丸中的生物可利用雄激素的浓度一无所知，因此实际上对大鼠或人的生物可用性雄激素浓度和精子发生之间的关系一无所知。 该项目的主要目的是识别和量化人睾丸的雄激素含量，评估静脉内雄激素的生物利用度，以实验确定可生物可用的内部雄激素雄激素浓度和精子发生之间的关系，并检查睾丸激素替代性替代性生物剂的影响和近代型和杂种的影响。