androstenedione

アンドロステンジオン

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/10/27 22:15:57」(JST)

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Not to be confused with 1-Androstenedione or Androstanedione.

Androstenedione

Systematic (IUPAC) name
4-Androstene-3,17-dione
Clinical data
Pregnancy cat.	?
Legal status	Schedule III (US)
Pharmacokinetic data
Metabolism	Liver
Identifiers
CAS number	63-05-8 Y
ATC code	None
PubChem	CID 6128
IUPHAR ligand	2860
DrugBank	DB01536
ChemSpider	5898 Y
UNII	409J2J96VR Y
ChEBI	CHEBI:16422 Y
ChEMBL	CHEMBL274826 Y
Chemical data
Formula	C19H26O2
Mol. mass	286.4
SMILES O=C4/C=C3/CC[C@@H]2[C@H](CC[C@@]1(C(=O)CC[C@H]12)C)[C@@]3(C)CC4
InChI InChI=1S/C19H26O2/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/h11,14-16H,3-10H2,1-2H3/t14-,15-,16-,18-,19-/m0/s1 Y Key:AEMFNILZOJDQLW-QAGGRKNESA-N Y
Y (what is this?)  (verify)

Androstenedione (also known as 4-androstenedione and 17-ketoestosterone) is a 19-carbon steroid hormone produced in the adrenal glands and the gonads as an intermediate step in the biochemical pathway that produces the androgen testosterone and the estrogens estrone and estradiol.

Synthesis

Steroidogenesis. Androstenedione is at center.

Androstenedione is the common precursor of male and female sex hormones. Some androstenedione is also secreted into the plasma, and may be converted in peripheral tissues to testosterone and estrogens.

Androstenedione can be synthesized in one of two ways. The primary pathway involves conversion of 17-hydroxypregnenolone to dehydroepiandrosterone by way of 17,20-lyase, with subsequent conversion of dehydroepiandrosterone to androstenedione via the enzyme 3-β-hydroxysteroid dehydrogenase. The secondary pathway involves conversion of 17-hydroxyprogesterone, most often a precursor to cortisol, to androstenedione directly by way of 17,20-lyase. Thus, 17,20-lyase is required for the synthesis of androstenedione, whether immediately or one step removed.

Androstenedione is further converted to either testosterone or estrogen. Conversion of androstenedione to testosterone requires the enzyme 17β-hydroxysteroid dehydrogenase, whereas conversion of androstenedione to estrogen (e.g., estrone and estradiol) requires the enzyme aromatase.

The production of adrenal androstenedione is governed by ACTH, whereas production of gonadal androstenedione is under control by gonadotropins. In premenopausal women, the adrenal glands and ovaries each produce about half of the total androstenedione(about 3 mg/day). After menopause, androstenedione production is about halved, due primarily to the reduction of the steroid secreted by the ovary. Nevertheless, androstenedione is the principal steroid produced by the postmenopausal ovary.

Endocrine function

In females, androstenedione is released into the blood by theca cells. The function of this is to provide androstenedione substrate for estrogen production in granulosa cells, since these cells lack 17,20 lyase required for androstenedione. Likewise, theca cells lack the enzyme aromatase required to make estrogens themselves. Thus, theca cells and granulosa cells work together to form estrogen.

Androstenedione as a supplement

History

Androstenedione was manufactured as a dietary supplement, often called andro (or andros) for short. Sports Illustrated credits Patrick Arnold for introducing androstenedione to the North American market. Andro was legal and able to be purchased over the counter, and, as a consequence, it was in common use in Major League Baseball throughout the 1990s by record-breaking sluggers like Mark McGwire. The supplement is banned by the World Anti-Doping Agency, and from the Olympic Games.

The International Olympic Committee in 1997 banned androstenedione and placed it under the category of androgenic-anabolic steroids.

Androstenedione is banned by the USOC and NCA but not by MLB and the NBA.

Barry R. McCaffrey, the director of the White House's Office of National Drug Control Policy, attempted to determine whether androstenedione could be classified as an anabolic steroid in July 1999. However, it could not because there is no proof of it promoting muscle growth.

On March 12, 2004, the Anabolic Steroid Control Act of 2004 was introduced into the United States Senate. It amended the Controlled Substance Act to place both anabolic steroids and prohormones on a list of controlled substances, making possession of the banned substances a federal crime. The law took effect on January 20, 2005. However, androstenedione was legally defined as an anabolic steroid, even though there is scant evidence that androstenedione itself is anabolic in nature.

On April 11, 2004, the United States Food and Drug Administration banned the sale of androstenedione, citing that the drug poses significant health risks commonly associated with steroids.

Androstenedione is currently banned by the U.S. military.

The Andro-Project

The "Andro-Project", conducted by medical researchers at East Tennessee State University, showed that the supplement "Andro"(androstenedione/androstenediol) does not increase muscle mass or strength.

Biological effects

Androstenedione has been shown to increase serum testosterone levels over an eight-hour period in men when taken as a single oral dose of 300 mg per day, but a dose of 100 mg had no significant effect on serum testosterone. However, serum levels of estradiol increased following both the 100 mg and 300 mg doses. The study also reported that the serum level of estrogens and testosterone produced varied widely between individuals. A 2006 review paper summarized several studies that examined the effect of androstenedione on strength training. At dosages of 50 mg or 100 mg per day, andro had no effect on muscle strength or size, or on body fat levels. One study used a daily dosage of 300 mg of androstenedione combined with several other supplements, and also found no increase in strength when compared to a control group that did not take the supplements. The review authors speculate that sufficiently high doses may indeed lead to increased muscle size and strength. However, due to the federal ban on androstenedione supplements, it is difficult to carry out new research on its positive and negative effects. The review authors conclude that individuals should not use androstenedione supplements due to the lack of evidence of beneficial effects, the wide variation in individual responses to the supplement, and the risk of unknown side-effects.

Because androstenedione is converted in part to estrogens, people taking this supplement may have estrogenic side-effects, although none of the studies cited above used a sufficiently high dosage to draw any conclusions.

In addition to its role as a precursor to testosterone in the body, androstenedione has androgenic properties in its own right, acting as a weak partial agonist of the androgen receptor. However, in the presence of full agonists like testosterone or dihydrotestosterone (DHT), due to its lower intrinsic activity in comparison, it has antagonistic properties, and can behave more like an antiandrogen like cyproterone.

Additional images

• Conversion of Androstendione to Estrone

• Dehydroepiandrosterone

• 17-Hydroxyprogesterone

• Testosterone

• Estrone

References

UpToDate Contents

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• 1. 多嚢胞性卵巣症候群におけるステロイドホルモン代謝 steroid hormone metabolism in polycystic ovary syndrome
• 2. 副腎アンドロゲンの測定 measurement of adrenal androgens
• 3. 思春期における多嚢胞性卵巣症候群の診断的評価 diagnostic evaluation of polycystic ovary syndrome in adolescents
• 4. Uncommon congenital adrenal hyperplasias
• 5. 副腎アンドロゲン過剰症 adrenal hyperandrogenism

English Journal

• Effects of polycyclic musks HHCB and AHTN on steroidogenesis in H295R cells.

• Li Z, Yin N, Liu Q, Wang C, Wang T, Wang Y, Qu G, Liu J, Cai Y, Zhou Q, Jiang G.SourceState Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, Beijing 100085, China.
• Chemosphere.Chemosphere.2013 Jan;90(3):1227-35. doi: 10.1016/j.chemosphere.2012.09.056. Epub 2012 Oct 17.
• 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-(γ)-2-benzopyran (HHCB) and 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN) are widely used in personal care products. Previous studies showed that HHCB and AHTN can be found in various environmental matrices and have poten
• PMID 23084589

• Enhanced screening efficiency for endocrine-disrupting chemicals in milk and powdered milk using UPLC/QTOF-MS by the introduction of dansyl chloride derivatisation.

• Wang HX, Zhou Y, Jiang QW.Sourcea Key Laboratory of Public Health Safety of Ministry of Education, School of Public Health, Fudan University , Shanghai 200032 , China.
• Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.Food Addit Contam Part A Chem Anal Control Expo Risk Assess.2013 Jan;30(1):166-80. doi: 10.1080/19440049.2012.720036. Epub 2012 Sep 11.
• This study developed and validated a sensitive analytical method for simultaneous screening of four classes of endocrine-disrupting chemicals (i.e. progestogens, androgens, oestrogens and phenols) in milk and powdered milk using ultra-performance liquid chromatography (UPLC) coupled with electrospra
• PMID 22963687

Japanese Journal

• Effect of Dietary Protein Levels on Sex Hormones in Growing Male Rats Kept under Constant Darkness

• HANAI Miho,ESASHI Takatoshi
• Experimental Animals 61(5), 555-561, 2012
• … Serum testosterone and androstenedione concentrations were lower in D-group rats fed the low-protein diet. … These results indicate that the suppression of gonadal development in D-group rats fed the low-protein diet was caused by low testosterone, which we attribute to the inhibition of synthesized androstenedione, a precursor of testosterone. … The present study showed that constant darkness and the low- protein diet inhibited the synthetic pathway from progesterone to androstenedione. …
• NAID 130001893582

• Isolation of Ovarian Components Essential for Growth and Development of Mammalian Oocytes In Vitro

• HIRAO Yuji
• Journal of Reproduction and Development 58(2), 167-174, 2012
• … Among ovarian factors, androstenedione was used to compensate for the absence of theca cells, and it promoted both follicular growth and acquisition of oocyte meiotic competence. …
• NAID 130001854955

• The Activity and Localization of 3β-hydroxysteroid Dehydrogenase/Δ5-Δ4 Isomerase and Release of Androstenedione and Progesterone by Uterine Tissues During Early Pregnancy and the Estrous Cycle in Pigs

• WOJCIECHOWICZ Bartosz,KOTWICA Genowefa,KOLAKOWSKA Justyna,FRANCZAK Anita
• Journal of Reproduction and Development 2012(0), 2012
• … We hypothesized that the uterus in pigs possesses active 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD) responsible for progesterone and androstenedione production, that uterine steroids may supplement the amount of steroid hormones produced by embryos and corpus luteum and that these steroids are necessary for maintenance of pregnancy. …
• NAID 130001854905

Related Links

• アンドロステンジオンとは - goo Wikipedia (ウィキペディア)

アンドロステンジオン(Androstenedione) は、副腎、性腺で生産される19炭素のステロイドホルモンで、テストステロン、エストロン、エストラジオールのそれぞれの生合成経路の中間生成物である 。 目次 1 生合成 2 サプリメントとしてのアンド ...

• 検査項目解説／臨床検査の三菱化学メディエンス

アンドロステンジオン androstenedione 保険点数 未収載 検査方法 RIA(チューブ固相法) 検査材料 血清 検体量(ml) 容器番号 保存方法 1 血清 0.4 01※チャート欄参照 冷蔵 報告所要日数 3～9日 基準値 ng/mL ※チャート欄参照 臨床的 意義 ...

Related Pictures

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★リンクテーブル★

リンク元	「副腎皮質ホルモン」「アンドロゲン」「アンドロステンジオン」

「副腎皮質ホルモン」

　　[★]

英

adrenocortical hormone

同

副腎皮質ステロイド adrenocorticoids

関

副腎皮質刺激ホルモン放出ホルモン、副腎皮質刺激ホルモン

ステロイド

関

副腎、副腎皮質、ステロイド、コルチコステロイド、ステロイドホルモン、コルチコイド。副腎皮質ホルモン剤

• 図：SP.891(組織),892(構造式)
• 副腎皮質の球状層、索状層、網状層で合成される

種類(主要なもののみ)

• 電解質コルチコイド

球状層から分泌される。アルドステロン

• 糖質コルチコイド

索状層から分泌される。コルチゾール

• 副腎アンドロジェン

網状層から分泌される。アンドロステンジオン

コレステロール cholesterol
↓CYP11A1
プレグネノロン pregnenolone	－－→ CYP17 17α-hydroxylase	17α-ヒドロキシプレグネノロン 17α-hydroxypregnenolone	－－→ CYP17 17α-hydroxylase	デヒドロエピアンドロステロン dehydroepiandrosterone DHEA
↓3β-HSD 3β-hydroxysteroid dehydrogenase		↓3β-HSD		↓3β-HSD
プロゲステロン progesterone	－－→ CYP17 17α-hydroxylase	17α-ヒドロキシプロゲステロン 17α-hydroxyprogesterone	－－→ CYP17 17α-hydroxylase	アンドロステンジオン androstenedione Δ4androstene-3,17-dion
↓CYP21 21-hydroxylase		↓CYP21 21-hydroxylase
デオキシコルチコステロン deoxycorticosterone		11-デオキシコルチゾール 11-deoxycortisol
↓CYP11B2　11β-hydroxylase		↓CYP11B1　11β-hydroxylase
コルチコステロン corticosterone		コルチゾール cortisol
↓CYP11B2 18-hydroxylase
18-ヒドロキシコルチコステロン 18-hydroxycorticosterone
↓CYP11B2 18-hydroxydehydrogenase
アルドステロン aldosterone
球状増 zona glomerulosa		索状層 zona fasciculata		網状層 zona reticularis

臨床関連

• 副腎皮質ホルモン過多：クッシング症候群
• 副腎皮質ホルモン欠乏：アジソン病
• 副腎皮質ホルモン合成異常：先天性副腎過形成

21-hydroxylaseが正常に機能しないことにより生じる (L.320)

薬理学

• 副腎皮質ホルモン製剤

副腎皮質から分泌されるホルモン (SP.895)

名称		血漿濃度 (ng/ml)	1日分泌量 (mg/day)
糖質コルチコイド	コルチゾール	40～180	15～20
	コルチコステロン	2～6	2～5
鉱質コルチコイド	アルドステロン	0.05～0.20	0.05～0.15
	11-DOC	0.05～0.30	0.10～0.20
副腎アンドロジェン	DHEA	2～8	7～15
	DHEA-S	1～4
	アンドロステンジオン	1～2	2～3

「アンドロゲン」

　　[★]

英

androgen

同

男性ホルモン male sex hormone

関

精巣性アンドロゲン

概念

• 男性ホルモン活性を有するものの総称。
• 男性ホルモン作用を有するステロイドホルモンの総称。

• 構造：C19ステロイド
• 副腎性：アンドロステンジオン androstenedione
• 精巣性：テストステロン testosterone

アンドロゲン

• テストステロン
• ジヒドロテストステロン (DHT)
• デヒドロエピアンドロステロン (DHEA)

• アンドロゲンは肝臓で不活化されるため、経口投与ではほとんど効果がない。

(http://ja.wikipedia.org/wiki/%E3%82%A2%E3%83%B3%E3%83%89%E3%83%AD%E3%82%B2%E3%83%B3)

性状

• ステロイド

産生組織

• 男性：精巣：ライディッヒ細胞
• 女性：卵巣：顆粒層細胞

• 卵胞内の卵胞上皮細胞で芳香環化されてエストロゲンに変換される。

• 両性：副腎皮質

作用

• アンドロゲンとは雄の副生殖器の発育および機能を促進し、二次性徴を発現させる作用をもつ物質の総称であり、数種類のホルモンからなる。

分泌の調整

• 男性：テストステロン、ジヒドロテストステロンの濃度上昇によりLHの分泌が抑制される。

臨床関連

• 先天性副腎皮質過形成

「アンドロステンジオン」

　　[★]

英

androstenedione

関

副腎、副腎皮質ホルモン、アンドロゲン