Recent highlights of research on androgen receptors in women

Abstract

In this brief review we present an outline of the current state of research on examples of hyperandrogenism that can be strongly associated with diverse modifications in the androgen signaling pathway. We discuss the most prominent clinical features of androgen excess and correlate them with studies on androgen receptor (AR) alterations. For the first time we summarize the confirmed localizations of all known AR receptors in women. The knowledge of ARs may be the basis for AR-targeted therapies of androgenic disorders in women, including malignancy, as it has recently been demonstrated for triple-negative breast cancer. Moreover, we summarize the structure and characterization of key AR splice variants, which could be involved in the androgenization in women.

Keywords: androgens; hyperandrogenism; protein splice variants; women; androgen receptors.

Fig. 1

The AR gene and its key protein transcripts. The AR is located on the X chromosome (locus: Xq11-Xq12) and includes 8 exons encoding 4 distinct domains: N-terminal domain (NTD), DNA-binding domain (DBD), hinge region, and ligand-binding domain (LBD). The above simplified scheme distinguishes: exons 1 to 8 of full-length AR (AR-FL), cryptic exons (i.e., CE1-4) of AR splice variants (AR-Vs) and AR45, and exon 9 of Ar^V567es. U - unique sequences not found in AR-FL. Adapted from [12].