Dihydrotestosterone

Not to be confused with Dihydrotachysterol.

Dihydrotestosterone

Systematic (IUPAC) name
(5S,8R,9S,10S,13S,14S,17S)-17-Hydroxy-10,13-dimethyl-1,2,4,5,6,7,8,9,11,12,14,15,16,17 -tetradecahydrocyclopenta[a]phenanthren-3-one
Clinical data
Pregnancy category	X
Routes of administration	Intramuscular, transdermal
Pharmacokinetic data
Bioavailability	Oral 0-2%
Metabolism	Hepatic
Excretion	Renal
Identifiers
CAS Number	521-18-6 Y
ATC code	A14AA01 (WHO)
PubChem	CID: 10635
IUPHAR/BPS	2856
DrugBank	DB02901 Y
ChemSpider	10189 Y
UNII	08J2K08A3Y Y
ChEBI	CHEBI:16330 Y
ChEMBL	CHEMBL27769 N
Chemical data
Formula	C19H30O2
Molecular mass	290.442 g/mol
SMILES O=C4C[C@@H]3CC[C@@H]2[C@H](CC[C@]1(C)[C@@H](O)CC[C@H]12)[C@@]3(C)CC4
InChI InChI=1S/C19H30O2/c1-18-9-7-13(20)11-12(18)3-4-14-15-5-6-17(21)19(15,2)10-8-16(14)18/h12,14-17,21H,3-11H2,1-2H3/t12-,14-,15-,16-,17-,18-,19-/m0/s1 Y Key:NVKAWKQGWWIWPM-ABEVXSGRSA-N Y
NY (what is this?)  (verify)

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 under brand names including Anabolex, Anaprotin, Andractim, Androlone, Gelovit, Neoprol, Pesomax, and Stanaprol, is used clinically as an androgen and anabolic steroid. Unlike testosterone and some anabolic steroids, DHT cannot be aromatized, and hence, has no risk of producing estrogenic effects such as gynecomastia.

Effects on sexual development

Chemical structure of testosterone. Compared with DHT, there is a double bond in the A ring (left).

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 5-α-reductase (5-AR) 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.

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.

Pathology

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.

Treatment for related conditions

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.

Metabolism

DHT is inactivated to 3α-androstanediol and 3β-androstanediol by the enzymes 3α-hydroxysteroid dehydrogenase and 3β-hydroxysteroid dehydrogenase, respectively.

Levels

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. As such, DHT is considered to be the major androgen of the prostate, although testosterone can mediate similar effects.

Derivatives

Synthetic derivatives of DHT employed as anabolic steroids include mesterolone (1α-methyl-DHT) and drostanolone (2α-methyl-DHT).

See also

• Finasteride
• Dutasteride
• Male pattern baldness
• Management of baldness
• Benign prostatic hyperplasia
• Membrane androgen receptor