Androgen receptor

The androgen receptor is an intracellular steroid receptor of the nuclear receptor super family that specifically binds testosterone and dihydrotestosterone.

Structure
Like all steroid receptors, the androgen receptor has several functional domains. Androgen receptors have a DNA binding domain, a hinge section, and the hormone binding domain. There is only one active form of the androgen receptor. Smaller forms represent proteolytic fragments that are not considered physiologically relevant. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.

Gene
The gene for the androgen receptor is located on the X chromosome at Xq11-12.

Function
In some cell types testosterone interacts directly with androgen receptors while in others testosterone is converted by 5-alpha-reductase to dihydrotestosterone, an even more potent agonist for androgen receptor activation. Examples are derivatives of the Wolffian duct for the former, and derivatives of the urogenital sinus, the urogenital tubercle, and hair follicles for the latter.

The first known mechanism of action for androgen receptors was direct regulation of gene transcription. After androgen binds to an androgen receptor, restructuring with dimerization follows and the activated receptor complex enters the nucleus and binds to DNA. Androgen receptors interact with other proteins in the nucleus so as to cause alterations in gene transcription. Often the change in transcription is an activation resulting in formation of more messenger RNA that interacts with ribosomes to produce specific proteins. One of the known target genes of androgen receptor activation is insulin-like growth factor I (IGF-1). Thus, changes in levels of specific proteins in cells is one way that androgen receptors control cell behavior.

More recently, androgen receptors have been shown to have a second mode of action. As has been also found for other steroid hormone receptors such as estrogen receptors, androgen receptors can have actions that are independent of their interactions with DNA. Androgen receptors interact with certain signal transduction proteins in the cytoplasm. Androgen binding to cytoplasmic androgen receptors can cause rapid changes in cell function independent of changes in gene transcription, such as changes in ion transport. Regulation of signal transduction pathways by cytoplasmic androgen receptors can indirectly lead to changes in gene transcription, for example, by leading to phosphorylation of other transcription factors.

Androgens cause slow epiphysis, or maturation of the bones, but more of the potent epiphysis effect comes from the estrogen produced by aromatization of androgens. Steroid users of teen age may find that their growth had been stunted by androgen and/or estrogen excess. People with too little sex hormones can be short during puberty but end up taller as adults as in androgen insensitivity syndrome or estrogen insensitivity syndrome.

AR deficiencies
The androgen insensitivity syndrome, formerly known as testicular feminization, is caused by a mutation of the Androgen Receptor gene located on the X chromosome (locus:Xq11-Xq12). The androgen receptor seems to affect neuron physiology and is defective in Kennedy disease.

Reference

 * 1)  "Testosterone activates mitogen-activated protein kinase and the cAMP response element binding protein transcription factor in Sertoli cells" by Charity Fix, Cynthia Jordan, Patricia Cano and William H. Walker in Proc Natl Acad Sci U S A (2004) volume 101 pages 10919-10924.
 * Speroff L, Glass RH, Kase NG: Clinical Gynecologic Endocrinology and Infertility. Sixth Ed. Lippincott Williams & Wilkins, Baltimore,MD, 1999.