androstenedione androstenedione androstenedione, or 4-androstenedione (abbreviated as a4 or δ4-dione), also known as androst-4-ene-3,17-dione, is an endogenous weak androgen steroid hormone and intermediate in the biosynthesis of estrone and of testosterone from dehydroepiandrosterone (dhea). it is closely related to androstenediol (androst-5-ene-3β,17β-diol). this article is about androstenedione the hormone. for other uses, see androstenedione (disambiguation). not to be confused with androstanedione, androstanediol, androstenediol, or androstadienol. androstenedioneclinical dataother namesa4; δ4-dione; androstenedione; androst-4-ene-3,17-dione; 4-androstene-3,17-dione; 17-ketotestosterone; 17-oxotestosteroneroutes ofadministrationby mouthdrug classandrogen; anabolic steroidatc codenonelegal statuslegal status us: schedule iii pharmacokinetic datametabolismliveridentifiers iupac name (8r,9s,10r,13s,14s)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1h-cyclopentaphenanthrene-3,17-dione cas number63-05-8 ypubchem cid6128iuphar/bps2860drugbankdb01536 ychemspider5898 yunii409j2j96vrkeggd00051chebichebi:16422 ychemblchembl274826 ycomptox dashboard (epa)dtxsid8024523 echa infocard100.000.504 chemical and physical dataformulac19h26o2molar mass286.415 g·mol−13d model (jsmol)interactive imagemelting point173–174 °c (343–345 °f) smiles o=c4/c=c3/cc2(cc1(c(=o)cc12)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 ykey:aemfnilzojdqlw-qaggrknesa-n y (verify) biological function androstenedione is a precursor of testosterone and other androgens, as well as of estrogens like estrone, in the body. in addition to functioning as an endogenous prohormone, androstenedione also has weak androgenic activity in its own right. androstenedione has been found to possess some estrogenic activity, similarly to other dhea metabolites. however, in contrast to androstenediol, its affinity for the estrogen receptors is very low, with less than 0.01% of the affinity of estradiol for both the erα and erβ. adrenarche in children aged 6 to 8 years old, there is a rise in androstenedione secretion along with dhea during adrenarche. this rise in androstenedione and dhea is hypothesized to play a crucial role for learning social, cultural and ecological skills, such as the development and understanding of sexual attraction. furthermore, it is thought that androstenedione plays a role in levels of aggression and competition in boys, as a positive correlation between the two were observed, while testosterone levels were below detection. biochemistry biosynthesis steroidogenesis. androstenedione is at center. androstenedione is the common precursor of the androgen and estrogen sex hormones. androstenedione can be biosynthesized in one of two ways. the primary pathway involves conversion of 17α-hydroxypregnenolone to dhea by way of 17,20-lyase, with subsequent conversion of dhea to androstenedione via the enzyme 3β-hydroxysteroid dehydrogenase. the secondary pathway involves conversion of 17α-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 produced in the adrenal glands and the gonads. the production of adrenal androstenedione is governed by adrenocorticotrophic hormone (acth), whereas production of gonadal androstenedione is under control by the 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. some androstenedione is also secreted into the plasma, and may be converted in peripheral tissues to testosterone and estrogens. production rates, secretion rates, clearance rates, and blood levels of major sex hormones sex sex hormone reproductivephase bloodproduction rate gonadalsecretion rate metabolicclearance rate reference range (serum levels) si units non-si units men androstenedione – 2.8 mg/day 1.6 mg/day 2200 l/day 2.8–7.3 nmol/l 80–210 ng/dl testosterone – 6.5 mg/day 6.2 mg/day 950 l/day 6.9–34.7 nmol/l 200–1000 ng/dl estrone – 150 μg/day 110 μg/day 2050 l/day 37–250 pmol/l 10–70 pg/ml estradiol – 60 μg/day 50 μg/day 1600 l/day <37–210 pmol/l 10–57 pg/ml estrone sulfate – 80 μg/day insignificant 167 l/day 600–2500 pmol/l 200–900 pg/ml women androstenedione – 3.2 mg/day 2.8 mg/day 2000 l/day 3.1–12.2 nmol/l 89–350 ng/dl testosterone – 190 μg/day 60 μg/day 500 l/day 0.7–2.8 nmol/l 20–81 ng/dl estrone follicular phase 110 μg/day 80 μg/day 2200 l/day 110–400 pmol/l 30–110 pg/ml luteal phase 260 μg/day 150 μg/day 2200 l/day 310–660 pmol/l 80–180 pg/ml postmenopause 40 μg/day insignificant 1610 l/day 22–230 pmol/l 6–60 pg/ml estradiol follicular phase 90 μg/day 80 μg/day 1200 l/day <37–360 pmol/l 10–98 pg/ml luteal phase 250 μg/day 240 μg/day 1200 l/day 699–1250 pmol/l 190–341 pg/ml postmenopause 6 μg/day insignificant 910 l/day <37–140 pmol/l 10–38 pg/ml estrone sulfate follicular phase 100 μg/day insignificant 146 l/day 700–3600 pmol/l 250–1300 pg/ml luteal phase 180 μg/day insignificant 146 l/day 1100–7300 pmol/l 400–2600 pg/ml progesterone follicular phase 2 mg/day 1.7 mg/day 2100 l/day 0.3–3 nmol/l 0.1–0.9 ng/ml luteal phase 25 mg/day 24 mg/day 2100 l/day 19–45 nmol/l 6–14 ng/ml notes and sources notes: "the concentration of a steroid in the circulation is determined by the rate at which it is secreted from glands, the rate of metabolism of precursor or prehormones into the steroid, and the rate at which it is extracted by tissues and metabolized. the secretion rate of a steroid refers to the total secretion of the compound from a gland per unit time. secretion rates have been assessed by sampling the venous effluent from a gland over time and subtracting out the arterial and peripheral venous hormone concentration. the metabolic clearance rate of a steroid is defined as the volume of blood that has been completely cleared of the hormone per unit time. the production rate of a steroid hormone refers to entry into the blood of the compound from all possible sources, including secretion from glands and conversion of prohormones into the steroid of interest. at steady state, the amount of hormone entering the blood from all sources will be equal to the rate at which it is being cleared (metabolic clearance rate) multiplied by blood concentration (production rate = metabolic clearance rate × concentration). if there is little contribution of prohormone metabolism to the circulating pool of steroid, then the production rate will approximate the secretion rate." sources: see template. metabolism androstenedione is converted to either testosterone or estrone. conversion of androstenedione to testosterone requires the enzyme 17β-hydroxysteroid dehydrogenase. androstenedione is released into the blood by theca cells. conversion of androstenedione to estrone requires the enzyme aromatase. androstenedione is a substrate for estrogen production in granulosa cells which produce aromatase. thus, theca cells and granulosa cells work together to form estrogens. androstanedione is a 5α-reduced metabolite of 4-androstenedione which serves as an intermediate in the biosynthesis of the androgen and neurosteroid androsterone. levels levels are normally 30–200 ng/dl (1.0–7.0 nmol/l) in females and 40–150 ng/dl (1.4–5.2 nmol/l) in males. in premature infants, serum androstenedione levels hover between 80 and 446 ng/dl. in full-term newborns, levels range from 20 to 290 ng/dl, and between 1 month and 1 year old, serum levels typically stay at less than 69 ng/dl. serum levels of androstenedione greater than or equal to 500 ng/dl may indicate the presence of an adrenal or gonadal tumor. pharmacology 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, androstenedione 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 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. medical use under the brand name metharmon-f and in combination with sex steroids (pregnenolone, testosterone, estrone, androstenediol) and thyroid hormone (desiccated thyroid), androstenedione is or has been marketed for medical use in thailand. chemistry