青春期阴茎增大的关键分子机制：雄激素—赖氨酰氧化酶—白膜重塑的调控研究

阴茎短小是临床上无法解决的难题，亟需阐明阴茎增大的关键机制，以便从全新的角度提供治疗措施。已有研究证实：男性雄激素的水平在青春期前后剧烈变化；白膜重塑系阴茎快速发育的重要机制。我们前期研究表明：青春期后，大鼠阴茎赖氨酰氧化酶(Lysyl Oxidase, LOX)的水平显著下降；青春期及成年大鼠进行抗LOX治疗后，阴茎均显著延长，且勃起功能不受影响。由此我们提出假设：在大鼠的阴茎发育过程中，雄激素与LOX共同导致白膜重塑促进阴茎增大，其机制与TGF-β信号通路相关。为验证此假设，本项目围绕“不同周龄大鼠雄激素及LOX水平变化”，“雄激素与LOX对阴茎白膜重塑的影响”，“利用基因敲除小鼠研究雄激素—TGF-β信号通路—LOX在白膜重塑中的机制”等问题开展一系列的基础研究。力争阐明青春期阴茎增大的关键机制，为阴茎短小的患者提供新的治疗思路。

Micropenis is an unsolved problem in clinical practice. To provide the treatment ideas from a new perspective, it is urgent to clarify the key mechanisms of penis enlargement in puberty. It has been proved that there is a drastic change in androgens during puberty, and tunica albuginea remodeling is the important mechanism in penis development. Our previous studies indicate that the Lysyl Oxidase (LOX) level of the rats’ penis decreased significantly after puberty, and the adult rats’ penis is prolonged significantly after anti-LOX treatment but the erectile function is not affected. So, we hypothesize: LOX and androgen lead to remodeling of the tunica albuginea and further promote penis enlargement, which may be regulated via TGF-β pathway in rat's penis development. To verify this hypothesis, the following specific aims are proposed: (1) determine the LOX and androgen levels in rats of different ages; (2) explore the effect of androgen and LOX on tunica albuginea remodeling; (3) delineate the cascade of TGF-β pathway in penis development using gene knockout mice. The answers to the above aims will provide us with novel insight of penis development, which may provide new treatment ideas for patients with micropenis.