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Dihydrotestosterone

Dihydrotestosterone

Overview
Dihydrotestosterone (DHT) Full name: 5α-Dihydrotestosterone, abbreviating to 5α-DHT; INN
International Nonproprietary Name
An International Nonproprietary Name is the official non-proprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...

: androstanolone is a biologically active metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. A secondary metabolite is not directly involved in those processes, but usually has...

 of the hormone
Hormone
A hormone is a chemical released by one or more cells that affects cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. It is essentially a chemical messenger that transports a signal from one cell to another. All multicellular organisms...

 testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands. It is the principal male sex hormone and an anabolic steroid.In men,...

, formed primarily in the prostate gland
Prostate
The prostate is a compound tubuloalveolar exocrine gland of the male mammalian reproductive system. Females do not have prostate glands...

, testes, hair follicle
Hair follicle
A hair follicle is a part of the skin that grows hair by packing old cells together. Attached to the follicle is a sebaceous gland, a tiny sebum-producing gland found everywhere except on the palms, lips and soles of the feet...

s, and adrenal gland
Adrenal gland
In mammals, the adrenal glands are the star-shaped endocrine glands that sit on top of the kidneys; their name indicates that position...

s by the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...

 5α-reductase
5-alpha reductase
5-Alpha reductase is an enzyme involved in steroid metabolism.-Function:It converts testosterone, the male sex hormone, into the more potent dihydrotestosterone:Note the major difference — the Δ4,5 double-bond on the A ring...

 by means of reducing the 4,5 double-bond. Dihydrotestosterone belongs to the class of compounds called androgens, also commonly called androgenic hormones or testoids.
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Encyclopedia
Dihydrotestosterone (DHT) Full name: 5α-Dihydrotestosterone, abbreviating to 5α-DHT; INN
International Nonproprietary Name
An International Nonproprietary Name is the official non-proprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...

: androstanolone is a biologically active metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. A secondary metabolite is not directly involved in those processes, but usually has...

 of the hormone
Hormone
A hormone is a chemical released by one or more cells that affects cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. It is essentially a chemical messenger that transports a signal from one cell to another. All multicellular organisms...

 testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands. It is the principal male sex hormone and an anabolic steroid.In men,...

, formed primarily in the prostate gland
Prostate
The prostate is a compound tubuloalveolar exocrine gland of the male mammalian reproductive system. Females do not have prostate glands...

, testes, hair follicle
Hair follicle
A hair follicle is a part of the skin that grows hair by packing old cells together. Attached to the follicle is a sebaceous gland, a tiny sebum-producing gland found everywhere except on the palms, lips and soles of the feet...

s, and adrenal gland
Adrenal gland
In mammals, the adrenal glands are the star-shaped endocrine glands that sit on top of the kidneys; their name indicates that position...

s by the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...

 5α-reductase
5-alpha reductase
5-Alpha reductase is an enzyme involved in steroid metabolism.-Function:It converts testosterone, the male sex hormone, into the more potent dihydrotestosterone:Note the major difference — the Δ4,5 double-bond on the A ring...

 by means of reducing the 4,5 double-bond. Dihydrotestosterone belongs to the class of compounds called androgens, also commonly called androgenic hormones or testoids. Androgens are part of the biology of gender
Biology of gender
The biology of gender is scientific analysis of the physical basis for behavioural differences between men and women. It is more specific than sexual dimorphism, which covers physical and behavioural differences between males and females of any sexually reproducing species, or sexual...

 by stimulating and controlling the development and maintenance of masculine characteristics. DHT is 3 times more potent than testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands. It is the principal male sex hormone and an anabolic steroid.In men,...

; testosterone is 5-10 times more potent than adrenal androgens.

While DHT is best known for its roles in causing male pattern hair loss and prostate
Prostate
The prostate is a compound tubuloalveolar exocrine gland of the male mammalian reproductive system. Females do not have prostate glands...

 problems, it is crucial to virilization and is necessary to mitigate estrogen
Estrogen
Estrogens are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone, their name comes from estrus/oistros + gen/gonos = to generate.Estrogens are used as part of some oral contraceptives, in estrogen replacement...

's effects in men.

Significance



DHT is produced by males in vivo
In vivo
In vivo refers to experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...

 and is responsible for the formation of male sex-specific characteristics. DHT is an important contributor to other characteristics generally attributed to males, including facial and body hair growth, and deepening of the voice. DHT may also play a crucial role in both sex drive and the growth of muscle tissue. Unlike other androgens such as testosterone, DHT cannot be converted by the enzyme aromatase
Aromatase
Aromatase is an enzyme that is responsible for a key step in the biosynthesis of estrogens. Because estrogens also promote certain cancers and other diseases, aromatase inhibitors are frequently used to treat those diseases....

 to estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is the predominant sex hormone present in females; however, it is present in males, albeit at lower levels, as well. It represents the major estrogen in humans...

. It, therefore, is frequently used in research settings to distinguish between effects of testosterone caused by binding to the androgen receptor
Androgen receptor
The androgen receptor , also known as NR3C4 , is a type of nuclear receptor which is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone...

, and those caused by testosterone's conversion to estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is the predominant sex hormone present in females; however, it is present in males, albeit at lower levels, as well. It represents the major estrogen in humans...

 and subsequent binding to estrogen receptor
Estrogen receptor
Estrogen receptor refers to a group of receptors that are activated by the hormone 17β-estradiol . Two types of estrogen receptor exist: ER which is a member of the nuclear hormone family of intracellular receptors and the estrogen G protein coupled receptor GPR30 , which is a G-protein coupled...

s.

Pathology


DHT is the primary contributing factor in male-pattern baldness
Baldness
Baldness involves the state of lacking hair where it often grows, especially on the head. The most common form of baldness is a progressive hair thinning condition called androgenic alopecia or "male pattern baldness" that occurs in adult male humans and other species...

. Female-pattern baldness is more complex, and DHT is only one of many causes of women's hair loss. Women with increased levels of DHT may develop certain androgynous
Androgyny
Androgyny is a term derived from the Greek words ανήρ and γυνή that can refer to either of two related concepts about gender: the mixing of masculine and feminine characteristics, as in fashion statements; or the balance of "anima and animus" in psychoanalytic theory.-Androgyne:Androgyne derives...

 male secondary sex characteristics, including a deepened voice and facial hair. DHT may play a role in the development or exacerbation of benign prostatic hyperplasia
Benign prostatic hyperplasia
Benign prostatic hyperplasia also known as benign prostatic hypertrophy , benign enlargement of the prostate , and adenofibromyomatous hyperplasia, refers to the increase in size of the prostate in middle-age and elderly men...

, or BPH, and prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. The cancer cells may metastasize from the prostate to other parts of the body, particularly the bones and lymph nodes. Prostate cancer may cause pain, difficulty in urinating, problems...

, by enlarging the prostate gland. The role of DHT on the prostate is not completely understood. There are some theories that indicate that the combination of DHT with other changes in other hormones such as increasing estrogen may be a factor. There are theories that indicate DHT injections can actually be used to treat benign prostate hypertrophy. The clinical application of this theory is discussed in US patent 5,648,350 Dihydrotestosterone for use in androgenotherapy. As such more research is required and there are studies underway to help understand the role of DHT on the prostate.

DHT is also known to participate in the development in some cases of acne
Acne vulgaris
Acne vulgaris is a common skin condition, caused by changes in pilosebaceous units, skin structures consisting of a hair follicle and its associated sebaceous gland, via androgen stimulation. It is characterized by noninflammatory follicular papules or comedones and by inflammatory papules,...

.

Treatment


The drugs belonging to the group known as 5α-reductase inhibitors
5-alpha-reductase inhibitor
5α-reductase inhibitors are a group of drugs with antiandrogenic activity, used in the treatment of benign prostatic hyperplasia and androgenic alopecia...

 are used for treatment of problems stemming from DHT. This group includes finasteride
Finasteride
Finasteride is a synthetic antiandrogen that acts by inhibiting type II 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone...

 (sold under the names Proscar for BPH and Propecia for androgenic alopecia
Alopecia
Alopecia or hair loss is the medical description of the loss of hair from the head or body, sometimes to the extent of baldness. Unlike the common aesthetic depilation of body hair, alopecia tends to be involuntary and unwelcome, e.g., androgenic alopecia...

 as well as in generic formulation) and dutasteride
Dutasteride
Dutasteride is a 5-alpha-reductase inhibitor, a drug which inhibits the conversion of testosterone into dihydrotestosterone . It is used to treat conditions caused by DHT, such as benign prostatic hyperplasia...

(sold under the name Avodart). Dutasteride is three times more potent than finasteride inhibiting the type II enzyme and 100 times more potent than finasteride inhibiting the type I form of the DHT-producing enzyme. Dutasteride is not approved by the FDA for the treatment of Male Pattern Hair Loss and is approved at a dose of 0.5 mg a day for the treatment of prostate enlargement. While both the type I and type II enzymes are found in the hair follicle, there is a recent study that shows that type I is present in the human brain. The function of this enzyme in the brain is still unclear.

Currently, DHT supplementation is not used as a treatment for DHT/androgen deficiency.