Androgens are produced and metabolized in many tissues including the skin

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Androgen Production and Metabolism

There are many vital hormones in the human body. Of these hormones, the androgen groups of hormones are hydrophobic compounds. Androgens are steroids, which like all other steroids are primarily protein-bound in the plasma.

Androgen production and metabolism is essential to the development and distribution of hair in the human body. Androgens effect the conversion of vellus hair to terminal hair in the human body. The conversion of vellus to terminal hair is a normal biological process that begins at puberty, continues through adult life and slows down with reproductive ageing in both sexes.

Low levels of androgens of predominantly adrenal origin result in the adrenarchal growth of axillary and pubic hair in both men and women, whereas higher levels of androgens of both adrenal and gonadal source produce the adult male like terminal hair growth that can be seen in the beard, ears, nose, sternum and upper pubic triangle. If this male-like hair production occurs in a female, then the disease is called hirsutism. Hirsutism in turn can be the result of various other associated ailments. The most prevalent among them are traced to androgen production disorders.

The sources of androgen

There are three sources of androgen in women.

  • The ovaries
  • Adrenal glands
  • The peripheral layer of the skin is also a key supplier of androgen. But here the androgens are not produced from cholesterol. Rather the peripheral skin transforms weak androgens to more potent androgens.

The first two contain steroidogenic enzymes that initiate androgen biosynthesis from cholesterol.

The strength of an androgen is determined by the ability to bind to the androgen receptor. The weaker androgens contain a 17a-hydroxyl group for instance as in androstenedone and androstenediol. More potent androgens are those containing a 17-keto group, example being testosterone (T) and dihydrotestosterone (DHT).

Anrdogen production

The most common contributor to the plasma level of androgens in women is dehydroepiandrosterone sulfate (DHEAS) made in the adrenal glands. Complete androgen production from cholesterol is possible only in tissues that contain 3 ß-hydroxysteroid dehydrogenase as in the ovaries, adrenals and skin. However, other tissues can produce some amount of androgen as well. Relatively little testosterone is produced in women and what testosterone is produced is made in the ovaries.

The group of enzymes called the side-chain cleavage enzymes P450 is said to play a major role in androgen production in both the ovary and adrenal glands. However, there are other theories as well. Some recent research however suggests the transfer of cholesterol into mitochondria. This process is determined by a group of mitochondrial proteins, known as the steroidogenic acute regulatory proteins.

Hormones that play a key role in glandular steroidogenesis are the trophic pituitary hormones, adrenocorticotropic hormone (ACTH) and the gonadotropins like folliclestimulating hormone (FSH) and especially luteinizing hormone (LH). ACTH functions at the adrenals and LH primarily in the ovary to trigger steroidogenesis.

The process of androgen receptor binding requires a 17-0H group. The enzyme 1713-01dehydrogenase is found in various tissues and transforms the 17-keto group (as in androstenedione) to a 17-0H group (as in testosterone).

To convert testosterone (T) to dihydrotestosterone (DHT), a tissue must have the enzyme 5a-reductase. Since DHT is the most potent endogenous androgen, those tissues such as the skin, prostate, and liver that contain 5a-reductase has a local intracellular procedure for intensification of androgen activity. Although probably hepatic production accounts for DHT circulation, local production and activity also plays a major role in its actions. In fact, the joint effect of local synthesis of DHT and circulating DHT may be vital in androgenic bioactivity.

Though ACTH from the pituitary primarily regulates adrenal androgen secretion, there are other control factors as well. The central nervous system (CNS) controls the pituitary production of ACTH. The CNS simultaneously regulates both ovarian and adrenal androgen synthesis. It’s a complex process that involves gonadotropin-releasing hormones, FSH and LH etc. and has a major function in the menstrual cycle of women.

Androgen circulation

Most androgens, like other steroids, are mainly bound in the plasma by four proteins. Out of these four proteins the cortisol-binding globulin and acid a2-glycoprotein are less significant, while the sex hormone-binding globulin SHBG and albumin are vital to androgen binding and transport.

Androgen production in the peripheral layers of the skin

This is a complex process within the skin’s androgen receptive tissues (such as the hair follicle) wherein testosterone is converted to DHT by 5a-reductase. The hair follicle is sensitive to androgen action in various ways and this plays a key role in the development of human hair. The process can be affected by the regional variations in androgen metabolizing enzymes in the skin. Skin parts that display androgen-dependent development of terminal hair have the local ability to produce DHT from testosterone and DHEA. This begins at puberty.