Androgen receptor

Human androgen receptor and androgen binding

androgen receptor sequence

Androgen Receptor (AR) is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in the cytoplasm and then moving into the nucleus. The androgen receptor is involved in a complex signal transduction pathway that ultimately results in greater expression of specific genes. All anabolic and androgenic effects of testosterone and dihydrotestosterone are mediated through the androgen receptor. It plays a crucial role in the development and maintenance of male sexual characteristics, muscle mass, bone density, and other physiological functions.

Structure

The androgen receptor is a protein that consists of several domains critical for its function: the N-terminal domain, DNA-binding domain (DBD), hinge region, and ligand-binding domain (LBD). The N-terminal domain is responsible for the transcriptional activation of target genes. The DNA-binding domain binds to specific DNA sequences known as androgen response elements (AREs) in the promoter region of target genes. The ligand-binding domain binds androgens, which triggers a conformational change that allows the receptor to interact with coactivators and the transcriptional machinery.

Function

Upon binding to its ligands, testosterone or dihydrotestosterone, the androgen receptor undergoes a conformational change that allows it to dimerize and translocate into the nucleus. Once in the nucleus, the receptor binds to AREs in the promoter regions of target genes, recruiting various coactivators and the transcriptional machinery to initiate transcription of these genes. The genes activated by the androgen receptor are involved in a wide range of physiological processes, including the development of male secondary sexual characteristics, spermatogenesis, muscle growth, and bone density.

Clinical Significance

The androgen receptor plays a significant role in the development of prostate cancer, as the growth of prostate cancer cells is often driven by androgens. Androgen deprivation therapy, which reduces levels of androgens or blocks their binding to the androgen receptor, is a common treatment for prostate cancer. Mutations in the androgen receptor gene can lead to androgen insensitivity syndrome (AIS), a condition that affects sexual development in males, resulting in the partial or complete inability of cells to respond to androgens.

Research

Research on the androgen receptor continues to uncover its role in health and disease. Studies are exploring the use of selective androgen receptor modulators (SARMs) that selectively activate the androgen receptors in certain tissues, aiming to achieve the beneficial effects of androgens without the side effects. Understanding the complex interactions between the androgen receptor and other signaling pathways also offers potential for new therapeutic targets in diseases such as prostate cancer, muscle wasting, and osteoporosis.

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