Perspective：Recent advances in the study of testicular nuclear receptor 4

Testicular nuclear receptor 4 （TR4）, also known as NR2C2 （nuclear receptor subfamily 2, group C, member 2）, is a transcriptional factor and a member of the nuclear receptor family. TR4 was initially cloned from human and rat hypothalamus, prostate, and testes libraries. For almost two decades, its spe- cific tissue distribution, genomic organization, and chromosomal assignment have been well investi. gated in humans and animals. However, it has been very difficult to study TR4＇s physiological functions due to a lack of specific ligands. Gene knock-out animal techniques provide an alternative approach for defining the biological functions of TR4. In vivo studies of TR4 gene knockout mice （TR4-/-） found that they display severe spinal curvature, subfertility, premature aging, and prostate prostatic intraepithe. lial neoplasia （PIN） development. Upstream modu- lators, downstream target gene regulation, feedback mechanisms, and differential modulation mediated by the recruitment of other nuclear receptors and coregu｜ators have been identified in studies using the TR4-~- phenotype. With the establishment of a tissue-specific TR4-/- mouse model, research on ＂I＇R4 will be more convenient in the future.