The role of the Androgen Receptor
Androgen receptor, abbreviated as AR and also referred to as NR3C4, is a kind of nuclear receptor. It is the fourth member of group C in the subfamily 3 of nuclear receptors. The androgen receptor gets activated when it binds to androgenic hormones, such as testosterone. The receptor binds to testosterone and also dihydrotestosterone in the cytoplasm of a cell and then trans-locates into its nucleus.
Androgen receptor in humans is encoded in the AR gene. It is found at Xq11-12 of the X chromosome. The receptor has an important function and its inefficiency or malfunction can cause complications. Deficiencies related to androgen receptor can lead to androgen insensitivity syndrome or testicular feminization. This is mostly caused due to a mutation of androgen receptor. The receptor affects physiology of neurons. Anomalies in the role of the receptor can cause other disorders.
Function of Androgen Receptor
The primary role of androgen receptor is to serve as transcription factor for DNA-binding to regulate gene expression. Regulation of genes by androgen hormones is crucial for development of male sexual characteristics. In a way, the receptor plays a role in determining the phenotype.
Androgen receptor plays a critical role in development of many types of cells. Some types of cells have testosterone directly interacting with the androgen receptors. In other types of cells, testosterone gets converted to dihydrotestosterone by 5-alpha-reductase. In such cells, dihydrotestosterone becomes the activator of the androgen receptor and hence triggers the function. Testosterone mainly activates the receptor in Wolffian duct. Dihydrotestosterone mainly activates the receptors in hair follicles, urogenital sinus and urogenital tubercle. Testosterone becomes the main hormone to influence the primary sexual traits of males. Dihydrotestosterone determines or influences the secondary sexual characteristics of males.
Androgens are potent hormones and play a major role in influencing overall growth and development. The hormones can slow down the process epiphysis, which is maturation of bones. Aromatization of the androgen hormones can negatively affect growth and development. Androgens can get converted to estrogens through aromatization and this can cause serious epiphysis, thereby stunting the growth of men during their teens or adolescence. Those who have a dearth of sex hormones during puberty are vulnerable to slow growth but it can get remedied during early adulthood. This is common among those who have estrogen or androgen insensitivity syndrome.
The androgen receptor plays an important role in males. It is also important for female fertility. Androgen receptor plays a vital role in the development of ovarian follicles. It helps to attain full functionality and also influences ovulation. The androgen receptor and its function works through neuroendocrine and intra-ovarian mechanisms.
Androgen receptor plays an important role in the maintenance of skeletal integrity in men. Androgens are responsible for skeletal integrity and they work via the receptor. Androgen receptor regulates the secretion of androgens and also how well they are put to use at distinct stages of musculoskeletal development and recovery.
Androgen receptor has genomic and non-genomic functions. The main mechanism is the receptor directly regulating the gene transcription. As an androgen binds to the receptor, it triggers the conformational change. This leads to dissociation of heat shock proteins and its subsequent transport to the nucleus of the cell from cytosol. The activation of the receptor also causes dimerization. As the receptor binds to particular sequences of DNA and has a distinct hormone response, it interacts with different proteins in a cell nucleus and regulates certain gene transcriptions. The regulation could be containment or a trigger factor.
An activation of gene transcription can improve synthesis of the RNA messenger. One such important activation pertains to the gene controlling the IGF-1R or insulin-like growth factor 1 receptor. This actually controls cell behavior by regulating certain proteins. There are many target genes of the receptor and the kind of activation determines the subsequent function. Androgen receptor does not always target DNA or gene. Independent of any DNA sequence, the receptor can influence serum response factor. This protein targets and activates genes that regular growth of muscles. This is the basis of the development of SARMs or selective androgen receptor modulators.
SARMS and the Androgen receptor has secondary actions and functions as well. It can interact with some proteins that are involved in signal transduction in the cytoplasm of a cell. The receptor can hence influence quick changes in the functioning of a cell.