Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32603, USA.
School of BioSciences, The University of Melbourne, Victoria 3010, Australia.
Genes (Basel). 2020 Jan 16;11(1):106. doi: 10.3390/genes11010106.
Congenital anomalies in phalluses caused by endocrine disruptors have gained a great deal of attention due to its annual increasing rate in males. However, the endocrine-driven molecular regulatory mechanism of abnormal phallus development is complex and remains largely unknown. Here, we review the direct effect of androgen and oestrogen on molecular regulation in phalluses using the marsupial tammar wallaby, whose phallus differentiation occurs after birth. We summarize and discuss the molecular mechanisms underlying phallus differentiation mediated by sonic hedgehog () at day 50 pp and phallus elongation mediated by insulin-like growth factor 1 ( and insulin-like growth factor binding protein 3 (, as well as multiple phallus-regulating genes expressed after day 50 pp. We also identify hormone-responsive long non-coding RNAs (lncRNAs) that are co-expressed with their neighboring coding genes. We show that the activation of and , mediated by balanced androgen receptor (AR) and estrogen receptor 1 (ESR1) signalling, initiates a complex regulatory network in males to constrain the timing of phallus differentiation and to activate the downstream genes that maintain urethral closure and phallus elongation at later stages.
由于男性中这种先天畸形的发病率呈逐年上升趋势，内分泌干扰物引起的阴茎先天畸形引起了人们的极大关注。然而，内分泌驱动的异常阴茎发育的分子调控机制非常复杂，在很大程度上仍不清楚。在这里，我们使用有袋动物塔马尔沙袋鼠来回顾雄激素和雌激素对阴茎分子调节的直接作用，因为这种动物的阴茎分化发生在出生后。我们总结并讨论了 sonic hedgehog () 在 50 天龄后介导的阴茎分化、胰岛素样生长因子 1 () 和胰岛素样生长因子结合蛋白 3 () 介导的阴茎伸长，以及 50 天后表达的多个调节阴茎的基因的分子机制。我们还鉴定了与邻近编码基因共表达的激素反应性长非编码 RNA (lncRNA)。我们表明，雄激素受体 (AR) 和雌激素受体 1 (ESR1) 信号介导的 和 的激活，在雄性中启动了一个复杂的调控网络，以限制阴茎分化的时间，并激活维持尿道闭合和后期阴茎伸长的下游基因。
