Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL, USA.
Biol Reprod. 2020 May 26;102(6):1225-1233. doi: 10.1093/biolre/ioaa023.
Androgens are essential for penile development and for maintaining penile structural and functional integrity. Loss of androgen levels or function results in a decrease in smooth muscle content, accumulation of adipocytes in the corpora cavernosa, and inhibition of erectile function. Our previous studies with a mouse model (KiLHRD582G) of constitutive luteinizing hormone receptor activity also showed structural abnormalities in the penis caused by a decrease in smooth muscle content, accumulation of chondrocytes, and sexual dysfunction. As KiLHRD582G mice exhibit very high levels of testosterone at all postnatal ages, the goal of this study was to determine if the elevated androgen levels were responsible for the morphological changes in the penis. Implantation of testosterone capsules in wild-type mice at neonatal (2 weeks) and postpubertal (5 weeks) ages resulted in the accumulation of chondrocytes in the corpora cavernosa of the adult animals. Mice implanted with testosterone capsules at 2 weeks of age exhibited a 4-fold increase in serum testosterone with a 1.5-fold loss of smooth muscle at 24 weeks of age. Collagen content was unchanged. Only 57% of testosterone implanted mice were fertile at 24 weeks of age. Mice implanted with testosterone capsules at 5 weeks of age showed no decrease in smooth muscle content at 24 weeks, although serum testosterone levels were elevated 5-fold. Implantation with dihydrotestosterone also resulted in chondrocyte accumulation and a 2-fold loss in smooth muscle content. Together, these studies demonstrate that supraphysiological levels of androgens cause structural changes in the penile corpora cavernosa and impair fertility.
雄激素对于阴茎的发育和维持其结构和功能完整性至关重要。雄激素水平或功能的丧失会导致平滑肌含量减少、海绵体脂肪细胞堆积以及勃起功能障碍。我们之前使用一种促黄体激素受体活性（KiLHRD582G）的小鼠模型进行的研究也表明，由于平滑肌含量减少、软骨细胞堆积和性功能障碍，阴茎会出现结构异常。由于 KiLHRD582G 小鼠在所有新生后时期都表现出非常高的睾丸激素水平，因此本研究的目的是确定升高的雄激素水平是否是导致阴茎形态变化的原因。在新生（2 周）和青春期后（5 周）时期将睾丸激素胶囊植入野生型小鼠中，导致成年动物海绵体中软骨细胞的积累。在 2 周龄时植入睾丸激素胶囊的小鼠血清睾丸激素水平增加了 4 倍，24 周龄时平滑肌减少了 1.5 倍。胶原含量不变。在 24 周龄时，只有 57%的植入睾丸激素的小鼠具有生育能力。在 5 周龄时植入睾丸激素胶囊的小鼠在 24 周时没有出现平滑肌含量减少，尽管血清睾丸激素水平升高了 5 倍。植入二氢睾酮也会导致软骨细胞积累和平滑肌含量减少 2 倍。总之，这些研究表明，超生理水平的雄激素会导致阴茎海绵体的结构变化，并损害生育能力。
