|Systematic (IUPAC) name|
|ATC code||A14AA01 (WHO)|
|Molar mass||290.442 g/mol|
|(what is this?)|
Dihydrotestosterone (commonly abbreviated to DHT), or 5α-dihydrotestosterone (5α-DHT), also known as 5α-androstan-17β-ol-3-one, is a sex steroid and androgen hormone. The enzyme 5α-reductase synthesizes DHT from testosterone in the prostate, testes, hair follicles, and adrenal glands. This enzyme reduces the 4,5 double-bond of the testosterone. Relative to testosterone, DHT is much more potent as an agonist of the androgen receptor.
DHT is also known as androstanolone (INN) and stanolone (BAN), and is used clinically under brand names including Anabolex, Anaprotin, Andractim, Androlone, Gelovit, Neoprol, Pesomax, and Stanaprol as an androgen and anabolic steroid. Unlike testosterone and some anabolic steroids, DHT cannot be aromatized, and hence, has no risk of estrogenic side effects such as gynecomastia.
DHT has an affinity (Kd) of 0.25 to 0.5 nM for the human androgen receptor (AR), which is about 2- to 3-fold higher than that of testosterone (Kd = 0.4 to 1.0 nM). The EC50 of DHT for activation of the AR is 0.13 nM, which is about 5-fold higher than that of testosterone (EC50 = 0.66 nM). In bioassays, DHT has been found to be 2.5- to 10-fold more potent than testosterone. The half-life of DHT in the body (53 minutes) is longer than that of testostrone (34 minutes), and this may account for some of the potency difference. A study of transdermal DHT and testosterone treatment reported half-lives of 2.83 hours and 1.29 hours, respectively.
In men, approximately 5% of testosterone undergoes 5α-reduction to form the more potent androgen, dihydrotestosterone (DHT). DHT has two to three times greater androgen receptor affinity than testosterone and has 15-30 times greater affinity than adrenal androgens. The dissociation rate of testosterone from the receptor is five-fold faster than DHT. During embryogenesis DHT has an essential role in the formation of the male external genitalia, while in the adult DHT acts as the primary androgen in the prostate and in hair follicles.
An example illustrating the significance of DHT for the development of secondary sex characteristics is congenital 5α-reductase deficiency. This gene lesion can result in pseudohermaphroditism. This condition typically presents with underdeveloped male genitalia and prostate. These individuals are often raised as girls due to their lack of conspicuous male genitalia. In the onset of puberty, although their DHT levels remain very low, their testosterone levels elevate normally. Their musculature develops like that of other male adults. After puberty, men with this condition have a large deficiency of pubic and body hair, and no incidence of male pattern baldness. They also have no incidence of prostate cancer.
Unlike other androgens such as testosterone, DHT cannot be converted by the enzyme aromatase to estradiol. Therefore, it is frequently used in research settings to distinguish between the effects of testosterone caused by binding to the androgen receptor and those caused by testosterone's conversion to estradiol and subsequent binding to estrogen receptors.
DHT created locally at the site of hair follicles by 5α-reductase, and not systemic levels of DHT, is the primary causal factor in male pattern baldness that results from hair follicle miniaturisation. However, female hair loss is more complex, and DHT is only one of several possible causes. Women with increased levels of DHT may develop certain androgynous male secondary sex characteristics, including a deepened voice and facial hair. It was once believed that DHT played a role in the development and exacerbation of benign prostatic hyperplasia, as well as prostate cancer, but this has largely been disproven. Prostate growth and differentiation are highly dependent on sex steroid hormones, particularly DHT.
5α-Reductase inhibitors are commonly used for the treatment of two DHT-related conditions, male pattern baldness (MPB), and benign prostatic hyperplasia (BPH). Dutasteride is approved for the treatment of benign prostatic hyperplasia, and is prescribed off-label for the treatment of male pattern baldness, whereas finasteride is approved for both conditions. Dutasteride is three times more potent than finasteride in inhibiting the type II enzyme and 100 times more potent than finasteride in inhibiting the type I form of the DHT-producing enzyme. Both finasteride and dutasteride are potent inhibitors of the third isotype of the enzyme.
DHT is synthesized from testosterone by the enzyme 5α-reductase. It is inactivated to 3α-androstanediol and 3β-androstanediol by the enzymes 3α-hydroxysteroid dehydrogenase and 3β-hydroxysteroid dehydrogenase, respectively. Unlike testosterone, DHT cannot be aromatized, and therefore has no propensity for estrogenic effects.
Serum DHT levels are about 10% of those of testosterone, but levels in the prostate gland are several-fold higher than those of testosterone due to extensive conversion of testosterone into DHT by locally expressed 5α-reductase. Moreover, DHT is considerably more potent than testosterone as an androgen. As such, DHT is considered to be the major androgen of the prostate, although testosterone can mediate similar effects.
- Dihydrotestosterone ester
- Male pattern baldness
- Management of baldness
- Benign prostatic hyperplasia
- Membrane androgen receptor
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