Loveland K L, Dias V, Meachem S, Rajpert-De Meyts E
Monash Institute of Medical Research, Monash University, Clayton, Vic., Australia.
Int J Androl. 2007 Aug;30(4):377-84; discussion 384. doi: 10.1111/j.1365-2605.2007.00785.x.
Regulated transforming growth factor-beta (TGFbeta) superfamily signalling is an integral part of normal testicular development and the processes that enable the production of fertile sperm. Through shared utilization of receptors, signal transduction components and inhibitors, many ligands in this family exhibit functional overlaps; this facet of their function is critical to understand because these ligands are often co-expressed and, hence, they may compete with or compensate for one another, depending on the specific cellular context. This review describes particular germ cell maturation steps governed by bone morphogenetic proteins, glial cell line-derived neurotrophic factor and activins, focusing on data predominantly from rodent studies that implicate activin and other family members in modulation of gonocyte and spermatogonial stem cell development. We also review knowledge of the TGFbeta superfamily signalling components in the human testis, exploring their potential impact on the processes associated with disrupted gonocyte development and an enhanced risk of testicular cancer.
受调控的转化生长因子-β(TGFβ)超家族信号传导是正常睾丸发育以及产生可育精子过程的一个组成部分。通过共享受体、信号转导成分和抑制剂,该家族中的许多配体表现出功能重叠;了解其功能的这一方面至关重要,因为这些配体通常共表达,因此,根据特定的细胞环境,它们可能相互竞争或相互补偿。本综述描述了由骨形态发生蛋白、胶质细胞源性神经营养因子和激活素调控的特定生殖细胞成熟步骤,重点关注主要来自啮齿动物研究的数据,这些数据表明激活素和其他家族成员参与了生殖母细胞和精原干细胞发育的调节。我们还综述了人类睾丸中TGFβ超家族信号传导成分的知识,探讨了它们对与生殖母细胞发育受阻和睾丸癌风险增加相关过程的潜在影响。