Department of Urology, University of California, 400 Parnassus Avenue, San Francisco, CA, USA, 94143.
Department of Urology, University of California, 400 Parnassus Avenue, San Francisco, CA, USA, 94143.
Differentiation. 2021 Sep-Oct;121:1-12. doi: 10.1016/j.diff.2021.08.002. Epub 2021 Aug 14.
Mouse penile development is androgen-dependent. During development of male and female external genitalia, an internal ectodermal epithelial structure forms called the preputial lamina. At puberty the male preputial lamina canalizes to create the preputial space, effectively splitting into two layers: (a) the epithelial lining of the prepuce and (b) the surface epithelium of the penis. The female preputial lamina does not canalize, and instead remodels into the inverted U-shaped clitoral lamina of the adult female mouse. Androgen-dependent penile development was studied in transgenic mice with pathway-selective AR mutant transgenes through which AR signaling was activated either via the classical (AR-C) or the nonclassical pathway (AR-NC). Penile development and canalization of the preputial lamina was observed in AR-C and wild-type male mice naturally having both AR-C and AR-NC pathways. Conversely, clitoral development occurred in AR null (lacking both AR-C and AR-NC pathways) and AR-NC mice. The process of canalization of the preputial lamina seen in wild-type, AR-C and AR-C/AR-NC male mice involved cornification of the preputial lamina which involved up-regulation of keratin 10 and loricrin. Such up-regulation of these epidermal proteins was absent in the developing and adult clitoral lamina seen in wild-type female mice and AR-NC and AR null male (XY) mice. Thus, signaling through AR-C is sufficient to initiate and promote penile development and canalization of the preputial lamina, a process involving epithelial cornification.
鼠标阴茎的发育依赖于雄激素。在男性和女性外生殖器的发育过程中，形成了一种称为包皮内板的内部外胚层上皮结构。在青春期，雄性包皮内板管化以形成包皮腔，有效地分为两层：（a）包皮的上皮衬里和（b）阴茎的表面上皮。雌性包皮内板不管化，而是重塑为成年雌性小鼠的倒 U 形阴蒂包皮。通过具有途径选择性 AR 突变转基因小鼠研究了雄激素依赖性阴茎发育，其中 AR 信号通过经典（AR-C）或非经典途径（AR-NC）激活。在自然具有 AR-C 和 AR-NC 两种途径的 AR-C 和野生型雄性小鼠中观察到阴茎发育和包皮内板管化。相反，在 AR 缺失（缺乏 AR-C 和 AR-NC 两种途径）和 AR-NC 小鼠中发生阴蒂发育。在野生型、AR-C 和 AR-C/AR-NC 雄性小鼠中观察到的包皮内板管化过程涉及包皮内板的角化，其中涉及角蛋白 10 和兜甲蛋白的上调。在野生型雌性小鼠和 AR-NC 和 AR 缺失雄性（XY）小鼠中发育和成年的阴蒂包皮中不存在这些表皮蛋白的这种上调。因此，AR-C 的信号足以启动和促进阴茎发育和包皮内板的管化，这一过程涉及上皮角化。
