Understanding Androgen Receptors

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Androgen Receptor - A Key Factor in Hair Growth

Androgen receptors are a key factor in the hair growth process.

These intracellular steroid receptors specifically bind the two types of Androgens - testosterone and dihydrotestosterone (DHT) and this receptor binding allows the androgens to stimulate and regulate the development and maintenance of masculine characteristics in vertebrates.

Androgenetic alopecia is the result of androgenetic function and androgen receptors are at the center of androgenetic functions.
Structure of androgen receptors
Like all steroid receptors, androgen receptors also have several functional domains.

A domain (or structural domain) within a protein is a self-stabilizing element of the overall structure. And it often folds independently of the rest of the protein chain. It plays a crucial role in the biological function of the protein it belongs to. And its self-stabilizing characteristic enables it to be swapped between one protein and another.
The domains found in androgen receptors
The domains found in an androgen receptor are as follows -
  • A DNA binding domain
  • A hinge section
  • The hormone binding domain
Active form of androgen receptors
There is just one form of active androgen receptor. Smaller forms represent proteolytic fragments considered to be physiologically irrelevant.

Relation with progesterone receptor
The androgen receptor is most closely related to the progesterone receptor, an intracellular steroid receptor specifically binding progesterone. The relationship I so close that higher dosages of progestins can block the androgen receptor.

Progesterone is a steroid hormone involved in the female menstrual cycle and pregnancy. It is also involved in the embryogenesis of humans and other species.
Gene of androgen receptors
The gene coding for androgen receptors is located on the X chromosome at Xq11-12.

The X chromosome is one of the two sex-determining chromosomes (the other being the Y chromosome) in many animal species including mammals. It is a part of both XY and XO sex-determination systems.
Function of androgen receptors
There are some cell types where testosterone has direct interaction with androgen receptors. There are also some locations where testosterone is converted into dihydrotestosterone by 5-alpha-reductase before binding to androgen receptors.

Examples of the former phenomenon are derivatives of the embryogenic Wolffian duct in men - namely the rete testis, the efferent ducts, the epididymis, the vas deferens, the seminal vesicle, and the prostate. The examples of the latter are the derivatives of the urogenital sinus, urogenital tubercle, and hair follicles.

An androgen molecule's binding to an androgen receptor is followed with restructuring of the androgen receptor. The activated receptor-androgen complex enters the nucleus of the cell and binds to DNA. Androgen receptors interact with the other proteins in the nucleus and thus cause alterations in gene transcription.

Insulin-like growth factor I (IGF - 1) is one of the known genes targeted by androgen receptors. IGF-1 is a stimulator of cell proliferation that is known to modify hair follicle growth. So, you can see that a change in the levels of specific proteins in cells is the process, by which androgen receptors control cell behavior.

The receptors also have a second mode of action independent of DNA interaction. In this action mode, the receptors interact with certain signal transduction proteins (a process by which a cell converts one kind of signal or stimulus into another) in the cell cytoplasm.

Androgen binding to cytoplasmic androgen receptors results in rapid changes in cell function independent of gene transcription changes. The regulation of signal transduction pathways by these types of androgen receptors can indirectly cause gene transcription changes.
Androgen Insensitivity Syndrome or AIS (a.k.a. Androgen Resistance Syndrome)
This refers to a set of disorders of sexual differentiation resulting from mutations of the gene encoding the androgen receptor. Sexual differentiation means the process of development of the differences between males and females.

The nature of the resulting problem
The nature of the resulting problem depends on the structure and sensitivity of the abnormal receptor. The most common form of AIS involves variable degrees of undervirilization and/or infertility in persons of either sex.

Undervirilization means inadequate virilization. Virilization is the development of changes making a male body different from a female body. Most of these changes are produced by androgens.

Infertility means one's inability to naturally conceive a child or to carry a pregnancy to full term.