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Dihydrotestosterone

 

Dihydrotestosterone

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 Registry Number  Y
ATC code A14
PubChem CID:
IUPHAR/BPS
DrugBank  Y
ChemSpider  Y
UNII  Y
ChEBI  Y
ChEMBL  N
Chemical data
Formula C19H30O2
Molecular mass 290.442 g/mol
 N   

Dihydrotestosterone (commonly abbreviated to DHT), or 5α-dihydrotestosterone (5α-DHT), also known as androstanolone (5α-androstan-17β-ol-3-one) as well as 17β-hydroxy-5α-androstan-3-one, is a sex steroid and androgen hormone. The enzyme 5α-reductase synthesizes DHT in the prostate, testes, hair follicles, and adrenal glands. This enzyme reduces the 4,5 double-bond of the hormone testosterone.

Contents

  • Effects on sexual development 1
  • Pathology 2
  • Treatment for related conditions 3
  • Metabolism 4
  • See also 5
  • References 6

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.[1] The dissociation rate of testosterone from the receptor is five-fold faster than DHT.[2] 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.[3]

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.[4] 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.[4] 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.[5]

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.[6]

Pathology

DHT is the primary contributing factor in male pattern baldness that results from hair follicle miniaturisation.[7][8] However, female hair loss is more complex, and DHT is only one of several possible causes.[9] Women with increased levels of DHT may develop certain androgynous male secondary sex characteristics, including a deepened voice and facial hair. DHT plays a role in the development and exacerbation of benign prostatic hyperplasia, as well as prostate cancer, by enlarging the prostate gland.[10] Prostate growth and differentiation are highly dependent on sex steroid hormones, particularly DHT.[11]

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.[12]

Metabolism

DHT is inactivated to 3α-androstanediol and 3β-androstanediol by the enzymes 3α-hydroxysteroid dehydrogenase and 3β-hydroxysteroid dehydrogenase, respectively.[13]

See also

References

  1. ^ Hemat RAS (2004). Principles Of Orthomolecularism. Urotext. p. 426.  
  2. ^ Grino, P. B.; Griffin, J. E.; Wilson, J. D. (1990). "Testosterone at high concentrations interacts with the human androgen receptor similarly to dihydrotestosterone". Endocrinology 126 (2): 1165–1172.  
  3. ^ Amory JK, Anawalt BD, Matsumoto AM, Page ST, Bremner WJ, Wang C, Swerdloff RS, Clark RV (June 2008). "The effect of 5alpha-reductase inhibition with dutasteride and finasteride on bone mineral density, serum lipoproteins, hemoglobin, prostate specific antigen and sexual function in healthy young men". J. Urol. 179 (6): 2333–8.  
  4. ^ a b "Androgens and the Evolution of Male-Gender Identity among Male Pseudohermaphrodites with 5α-Reductase Deficiency". New England Journal of Medicine 300: 1233–1237.  
  5. ^ Marks LS (2004). "5α-reductase: history and clinical importance". Rev Urol. 6 Suppl 9: S11–21.  
  6. ^ Swerdloff RS, Wang C (October 1998). "Dihydrotestosterone: a rationale for its use as a non-aromatizable androgen replacement therapeutic agent". Baillieres Clin. Endocrinol. Metab. 12 (3): 501–6.  
  7. ^ Nordqvist C (2012-02-23). "What Is DHT (Dihydrotestosterone)? What Is DHT's Role In Baldness?". Medical News Today. 
  8. ^ "Male Pattern Baldness Causes". Hair Loss Health Center. WebMD, LLC. 
  9. ^ McAndrews PJ. "Women's Hair Loss / Causes of Hair Loss". American Hair Loss Association. 
  10. ^ "Prostate Enlargement - What Causes The Prostate To Enlarge?". ehealthMD. 
  11. ^ Freedland SJ, Isaacs WB, Platz EA, Terris MK, Aronson WJ, Amling CL, Presti JC, Kane CJ (October 2005). "Prostate size and risk of high-grade, advanced prostate cancer and biochemical progression after radical prostatectomy: a search database study". J. Clin. Oncol. 23 (30): 7546–54.  
  12. ^ Olsen EA, Hordinsky M, Whiting D, Stough D, Hobbs S, Ellis ML, Wilson T, Rittmaster RS (December 2006). "The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride". J. Am. Acad. Dermatol. 55 (6): 1014–23.  
  13. ^ Rizner TL, Lin HK, Peehl DM, Steckelbroeck S, Bauman DR, Penning TM (July 2003). "Human type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2) and androgen metabolism in prostate cells". Endocrinology 144 (7): 2922–32.  
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