Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Endocrinology. 2011 Sep;152(9):3504-14. doi: 10.1210/en.2011-0251. Epub 2011 Jul 5.
Why both testosterone (T) suppression and cryptorchidism reverse the block in spermatogonial differentiation in adult mice homozygous for the juvenile spermatogonial depletion (jsd) mutation has been a conundrum. To resolve this conundrum, we analyzed interrelations between T suppression, testicular temperature, and spermatogonial differentiation and used in vitro techniques to separate the effects of the two treatments on the spermatogonial differentiation block in jsd mice. Temporal analysis revealed that surgical cryptorchidism rapidly stimulated spermatogonial differentiation whereas androgen ablation treatment produced a delayed and gradual differentiation. The androgen suppression caused scrotal shrinkage, significantly increasing the intrascrotal temperature. When serum T or intratesticular T (ITT) levels were modulated separately in GnRH antagonist-treated mice by exogenous delivery of T or LH, respectively, the inhibition of spermatogonial differentiation correlated with the serum T and not with ITT levels. Thus, the block must be caused by peripheral androgen action. When testicular explants from jsd mice were cultured in vitro at 32.5 C, spermatogonial differentiation was not observed, but at 37 C significant differentiation was evident. In contrast, addition of T to the culture medium did not block the stimulation of spermatogonial differentiation at 37 C, and androgen ablation with aminoglutethimide and hydroxyflutamide did not stimulate differentiation at 32.5 C, suggesting that T had no direct effect on spermatogonial differentiation in jsd mice. These data show that elevation of temperature directly overcomes the spermatogonial differentiation block in adult jsd mice and that T suppression acts indirectly in vivo by causing scrotal regression and thereby elevating the testicular temperature.
为什么在成年雄性小鼠中，无论是睾丸酮（T）抑制还是隐睾症都能逆转幼年精原细胞耗竭（jsd）突变引起的精原细胞分化阻滞，这一直是个谜。为了解决这个难题，我们分析了 T 抑制、睾丸温度和精原细胞分化之间的相互关系，并使用体外技术来分离两种处理方法对 jsd 小鼠精原细胞分化阻滞的影响。时间分析表明，手术隐睾症迅速刺激精原细胞分化，而雄激素剥夺治疗则产生延迟和逐渐的分化。雄激素抑制导致阴囊收缩，显著增加了阴囊内温度。当 GnRH 拮抗剂处理的小鼠中通过外源性给予 T 或 LH 分别调节血清 T 和 ITT 水平时，精原细胞分化的抑制与血清 T 而不是 ITT 水平相关。因此，这种阻滞必须是由外周雄激素作用引起的。当将 jsd 小鼠的睾丸组织在 32.5°C 下进行体外培养时，观察不到精原细胞分化，但在 37°C 时则明显可见分化。相反，在 37°C 下，T 添加到培养基中并不会阻断精原细胞分化的刺激，而用氨基导眠能和羟基氟他胺进行雄激素剥夺也不会在 32.5°C 下刺激分化，这表明 T 对 jsd 小鼠的精原细胞分化没有直接作用。这些数据表明，温度升高可直接克服成年 jsd 小鼠的精原细胞分化阻滞，而 T 抑制在体内通过引起阴囊退化从而升高睾丸温度来间接作用。
