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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/04/28 00:10:42」(JST)

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Not to be confused with Dihydrotachysterol.

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.

Effects on sexual development

Testosterone. Note the major difference -- the 4,5 double-bond on the A ring (left).

In men, approximately 5% of testosterone undergoes 5α-reduction to form the more potent androgen, dihydrotestosterone. 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.^[5] 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.^[6]

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.^[7]

Pathology

DHT is the primary contributing factor in male pattern baldness.^[8]^[9] However, female hair loss is more complex, and DHT is only one of several possible causes.^[10] 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.^[11] Prostate growth and differentiation are highly dependent on sex steroid hormones, particularly DHT.^[12]

Benefits in chronic heart disease

DHT has beneficial effects on stable resting ischemia in patients with chronic heart disease. Chronic DHT administration in these patients significantly increases total exercise time, time to the onset of angina and time to 1 mm ST depression.^[13]

Treatment

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.^[14]

However, 5α-reductase inhibitors are thought to have persistent side effects that can continue after quitting the treatment, including diminished libido, erectile dysfunction and male breast cancer,^[15]^[16] and are suspected to have persistent cognitive side effects, including depression,^[17] brain fog and memory loss.^[16]

Metabolism

DHT is inactivated to 3α-androstanediol and 3β-androstanediol by the enzymes 3α-hydroxysteroid dehydrogenase and 3β-hydroxysteroid dehydrogenase, respectively.^[18] Be

References

^ Hemat RAS (2004). Principles Of Orthomolecularism. Urotext. p. 426. ISBN 1-903737-05-2.
^ 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. doi:10.1210/endo-126-2-1165. PMID 2298157. edit
^ 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. doi:10.1016/j.juro.2008.01.145. PMC 2684818. PMID 18423697.
^ http://dx.doi.org/10.1056/NEJM197905313002201
^ http://dx.doi.org/10.1056/NEJM197905313002201
^ Marks LS (2004). "5α-reductase: history and clinical importance". Rev Urol. 6 Suppl 9: S11–21. PMC 1472916. PMID 16985920.
^ 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. PMID 10332569.
^ Nordqvist C (2012-02-23). "What Is DHT (Dihydrotestosterone)? What Is DHT's Role In Baldness?". Medical News Today.
^ "Male Pattern Baldness Causes". Hair Loss Health Center. WebMD, LLC.
^ McAndrews PJ. "Women's Hair Loss / Causes of Hair Loss". American Hair Loss Association.
^ "Prostate Enlargement - What Causes The Prostate To Enlarge?". ehealthMD.
^ 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. doi:10.1200/JCO.2005.05.025. PMID 16234520.
^ Palusiński R, Barud W, Biłan A, Witczak A, Myśliński W, Hanzlik J: [Effect of dihydrotestosterone treatment on exercise induced ischemia in men with stable ischemic heart disease]. 2000 Aug;9(50):533-4.
^ 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. doi:10.1016/j.jaad.2006.05.007. PMID 17110217. Lay summary – IAHRS Hair Transplant & Hair Loss Info Center.
^ Irwig MS, Kolukula S (June 2011). "Persistent sexual side effects of finasteride for male pattern hair loss". J Sex Med 8 (6): 1747–53. doi:10.1111/j.1743-6109.2011.02255.x. PMID 21418145.
^ ^a ^b Traish AM, Hassani J, Guay AT, Zitzmann M, Hansen ML (March 2011). "Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients". J Sex Med 8 (3): 872–84. doi:10.1111/j.1743-6109.2010.02157.x. PMID 21176115.
^ Rahimi-Ardabili B, Pourandarjani R, Habibollahi P, Mualeki A (2006). "Finasteride induced depression: a prospective study". BMC Clin Pharmacol 6: 7. doi:10.1186/1472-6904-6-7. PMC 1622749. PMID 17026771.
^ 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. doi:10.1210/en.2002-0032. PMID 12810547.

UpToDate Contents

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1. 副腎アンドロゲンの測定 measurement of adrenal androgens
2. 男性生殖生理学 male reproductive physiology
3. 女性型脱毛症（女性のアンドロゲン性脱毛症）：病態、臨床的特徴および診断 female pattern hair loss androgenetic alopecia in women pathogenesis clinical features and diagnosis
4. 高齢男性におけるテストステロン欠乏症の概要 overview of testosterone deficiency in elderly men
5. ステロイド5 -α-レダクターゼ2欠乏症 steroid 5 alpha reductase 2 deficiency

English Journal

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French VA1, Codi King S2, Kumar A3, Northcott G4, McGuinness K5, Parry D2.
The Science of the total environment.Sci Total Environ.2015 Dec 1;536:639-47. doi: 10.1016/j.scitotenv.2015.07.114. Epub 2015 Aug 4.
The detection of microcontaminants in aquatic environments raises concerns about their potential to exert ecotoxicological effects and impact human health. In contrast to freshwater habitats, little information is available on environmental concentrations in urban estuarine and marine environments.
PMID 26247692

Sex chromosome complement determines sex differences in aromatase expression and regulation in the stria terminalis and anterior amygdala of the developing mouse brain.

Cisternas CD1, Tome K2, Caeiro XE2, Dadam FM2, Garcia-Segura LM3, Cambiasso MJ4.
Molecular and cellular endocrinology.Mol Cell Endocrinol.2015 Oct 15;414:99-110. doi: 10.1016/j.mce.2015.07.027. Epub 2015 Jul 29.
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Inhibition of adipogenic differentiation of human SGBS preadipocytes by androgen-regulated microRNA miR-375.

Kraus M1, Greither T1, Wenzel C1, Bräuer-Hartmann D2, Wabitsch M3, Behre HM4.
Molecular and cellular endocrinology.Mol Cell Endocrinol.2015 Oct 15;414:177-85. doi: 10.1016/j.mce.2015.07.026. Epub 2015 Jul 26.
Late-onset hypogonadism (LOH), defined as a combination of low serum testosterone (T) levels in combination with clinical signs and symptoms of androgen deficiency in ageing men, is nowadays a well-characterized disease. Testosterone therapy in males affected by hypogonadism leads to a significant d
PMID 26219823

Japanese Journal

男性型脱毛症総論 (特集臨床で役立つ毛髪治療update)

Pepars (98), 1-8, 2015-02
NAID 40020388480

Androgen receptor functions as a negative transcriptional regulator of DEPTOR, mTOR inhibitor

The Journal of Toxicological Sciences 40(6), 753-758, 2015
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Testosterone, dihydrotestosterone and estradiol are differentially associated with carotid intima-media thickness and the presence of carotid plaque in men with and without coronary artery disease

Endocrine Journal 62(9), 777-786, 2015
NAID 130005100643

Related Pictures

★リンクテーブル★

リンク元	「ジヒドロテストステロン」「DHT」「androstanolone」
拡張検索	「dihydrotestosterone level」

「ジヒドロテストステロン」

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[citation needed]
Clinical data
Pregnancy cat.	X
Legal status	?
Routes	Intramuscular, transdermal
Pharmacokinetic data
Bioavailability	Oral 0-2%
Metabolism	Hepatic
Excretion	Renal
Identifiers
CAS number	521-18-6
ATC code	A14AA01
PubChem	CID 10635
IUPHAR ligand	2856
DrugBank	DB02901
ChemSpider	10189
UNII	08J2K08A3Y
ChEBI	CHEBI:16330
ChEMBL	CHEMBL27769
Chemical data
Formula	C19H30O2
Mol. 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 ; Key:NVKAWKQGWWIWPM-ABEVXSGRSA-N ;
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