Roles of Androgen Receptor in Male and Female Reproduction: Lessons From Global and Cell‐Specific Androgen Receptor Knockout (ARKO) Mice

Abstract

ABSTRACT:The androgen receptor (AR), a member of the nuclear receptor superfamily, is a ligand-dependent transcription factor involved in regulating expression of an array of androgen-responsive genes. AR-mediated androgen actions play the important roles in male and female reproductive development and function. AR mutations can cause a diverse range of diseases, such as testicular feminization mutation (Tfm) syndrome, prostate cancer, and Kennedy's disease. However, because of a lack of genetic models, the molecular mechanisms involved in the physiological and pathological effects of androgen-AR function in male and female reproductive health remains largely unknown. To get a better insight into the molecular working mechanisms of the AR, a global and several cellspecific conditional knockout mouse models have been developed. These models are reviewed here, and the phenotypes of the different cell-specific androgen receptor knockout (ARKO) mice are compared with those of the global ARKO mice.

Steroid Receptors in the Uterus and Ovary

“…There are several reported lines of AR-null as well as mice with knock-in of mutated forms of AR (reviewed in Refs 281,282). Tfm mice were first described in 1970 and are a naturally existing androgen-resistant mutant 283 with an inactivating mutation of the Ar gene.…”

Blood-testis barrier and spermatogenesis: lessons from genetically-modified mice

“…Androgen receptor ( Ar ), a member of the steroid hormone receptor superfamily, mediates androgen action and plays an important role in male reproduction (reviewed in124125126127). In testes, Ar can be detected in Sertoli cells, peritubular myoid cells and cells in the interstitial spaces including Leydig cells and perivascular smooth muscle cells 495055565758.…”

The Stroma—A Key Regulator in Prostate Function and Malignancy

“…For example members of the fibroblast growth factor (FGF), insulin-like growth factor (IGF), epidermal growth factor (EGF), Wnt and hepatocyte growth factor (HGF) families apparently function as andromedins [7,8]. ARs in luminal epithelial cells maintain cell survival whereas AR in basal/intermediate epithelial cells suppress proliferation [9,10,11,12,13]. Estrogen receptor (ER) α is expressed in the prostate stoma and mediates secretion of stroma factors stimulating epithelial cells.…”