Description
Epiandrosterone is a steroid hormone with weak androgenic activity, derived from 5 α-androstane. It is a dehydroepiandrosterone metabolite and an androgen. It is a precursor of testosterone and estradiol with hypolipidemic and anabolic activities.
Chemical Properties
white to off-white crystalline powder
Uses
A steroid hormone that is present in normal human urine as a minor constituent , it is a less active 3β-isomer of the androgen Androsterone (A635535). Controlled Substance.
Application
Epiandrosterone presents some neurological activity since it can bind to the ?-aminobutyric acid (GABA)/benzodiazepine-receptor complex (GABA-RC), acting as a negative non-competitive modulator of GABA-RC, and signaling through the N-methyl-D-aspartate receptor.
It can also inhibit the pentose phosphate pathway, dilating blood vessels pre-contracted by partial depolarization.
Epiandrosterone can inhibit the thromboxane A2 synthesis in activated platelets, decrease plasma plasminogen activator inhibitor type 1, reduce tissue plasminogen activator antigen, improve insulin-like growth factor 1 serum levels, and increase the synthesis of cyclic guanosine monophosphate and nitric oxide.
In vitro assays demonstrate that this compound inhibits Junin virus replication vitro anti-adenovirus (AdV) activity.
Epiandrosterone affects glucose oxidation and interleukin-1 beta in in vitro pancreatic islets.
Definition
ChEBI: A 3beta-hydroxy steroid that is (5alpha)-androstane substituted by a beta-hydroxy group at position 3 and an oxo group at position 17.
Preparation
Epiandrosterone is naturally produced by the enzyme 5α-reductase from the adrenal hormone DHEA. Epiandrosterone can also be produced from the natural steroids androstanediol via 17β-hydroxysteroid dehydrogenase or from androstanedione via 3β-hydroxysteroid dehydrogenase.
Side effects
When taken by mouth: Epiandrosterone is POSSIBLY UNSAFE for most people when taken by mouth. Side effects include infertility, behavioral changes, hair loss, and breast development (in men). Epiandrosterone can also lead to liver damage and heart disease.
in vitro
it was reported that epi, at concentrations from 10 to 100 mm, decreased left-ventricular developed pressure (lvdp) and myocardial contraction rate dose-dependently. in addition, epi also increased cpp in isolated hearts, down-regulated levels of myocardial nadph and nitrite, as well as relaxed rat aortic rings in the dose-dependent manner. findings from whole cell clamp via electrophysiological analysis of single ventricular myocytes demonstrated that epi could reversibly block l-type channel currents carried by ba2+ in a dose-dependent manner with an ic50 of2 ± 6 m. moreover, epi, at a concentration of 30 mm, accelerated the decay of iba during depolarization, which suggested this agent as a l-type ca2+ channel antagonist with similar properties to those of 1, 4-dihydropyridine (dhp) ca2+ channel blockers. [1]
in vivo
in vivo tests were performed using g-6-pd-low c57l/j mouse erythrocytes. every other day, mice were orally administered with 450 or 900 mg/kg of tested agents including dhea, epi, pregnenolone (preg) and androstanedione (andr) for seven days (four doses). three hours after the final dose, mice were sacrificed. findings from blood samples suggested that g-6-pd activity had no significant changes, which might be caused by the lack of receptor sites for the steroids on the erythrocyte membrane. [2]
IC 50
blocking l-type calcium channels of ventricular myocytes with an ic50 of 42 ± 6 m.
Purification Methods
Purify epi-androsterone via the acetate, hydrolyse this and recrystallise it from CHCl3/hexane or aqueous EtOH. The acetate [1239-31-2] is purified by chromatography and when crystallised from pet ether has m 103-104o, []D +68.5o (c 1, CHCl3). The oxime has m 194-196o (from MeOH), []D +17.5o (c 6.2, CHCl3). The racemic ketone is sublimed at 130o/high vacuum and after two crystallisations from methylcyclohexane it gives prisms with m 161-162o (which changed crystal form at 140-145o). [Ruzicka & Wettstein Helv Chim Acta 18 1264 1935, Johnson et al. J Am Chem Soc 75 2275 1953, 78 6331 1956, Cordwell et al. J Chem. Soc 361 1953, Beilstein 8 IV 462.]
Mode of action
Epiandrosterone is a dehydroepiandrosterone metabolite and a precursor of testosterone and estradiol with hypolipidemic and anabolic property. Epiandrosterone, a potential neurosteroid, appears to bind to the gamma-aminobutyric acid (GABA)/benzodiazepine-receptor complex (GABA-RC), acting as a negative non-competitive modulator of GABA-RC as well as signal through the N-methyl-D-aspartate receptor. In addition this agent inhibits the pentose phosphate pathway (PPP) thereby dilating blood vessels pre-contracted by partial depolarization. Also, epiandrosterone inhibits the synthesis of thromboxane A2 in activated platelets, reduces plasma plasminogen activator inhibitor type 1 and tissue plasminogen activator antigen, increases serum levels of insulin-like growth factor 1 and increases cyclic guanosine monophosphate and nitric oxide synthesis. These effects may improve circulation in the microvasculature.
References
[1]gupte sa, tateyama m, okada t, oka m and ochi r. epiandrosterone, a metabolite of testosterone precursor, blocks l-type calcium channels of ventricular myocytes and inhibits myocardial contractility. j mol cell cardiol. 2002 mar; 34: 679- 88.
[2]calabrese ej, horton hm and leonard da. the in vivo effects of four steroids on glucose-6-phosphate dehydrogenase activity of c57l/j mouse erythrocytes. j. environ. sci. health. 1987; a22(6): 563-74.
[3]forrest ad, drewery j, fotherby k and laverty sg. a
