Disease relevance of Hombreol

• Estradiol (E2) and 5alpha-androstan-3alpha,17beta-diol (3alpha-diol) have been implicated in prostate hyperplasia in man and dogs, but neither of these steroids bind to androgen receptors (ARs) [1].
• Optic nerve head (ONH) astrocytes from patients with glaucomatous optic neuropathy exhibit increased production of 5alpha-androstane-3alpha,17beta-diol (3alpha-diol), a neuroactive metabolite of 5alpha-dihydrotestosterone (5alpha-DHT) [2].
• Virilization of the urogenital sinus of the tammar wallaby is not unique to 5alpha-androstane-3alpha,17beta-diol [3].
• Six experiments were carried out to determine whether dihydrotestosterone (5 alpha-androstan-17 beta-ol-3-one; DHT) acts to inhibit oestradiol (OE2)-induced lordosis behaviour after its metabolic conversion to 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-androstanediol, 3 alpha-Adiol) [4].
• Circulating levels of 5 alpha-androstane-3 alpha,17 beta-diol (diol) were measured in 24 elderly men (50-80 years) without prostatic tumours and compared with 32 patients (54-84 years) with benign prostatic hypertrophy (BPH) and 32 patients (51-85 years) with carcinoma of the prostate (Ca) [5].

High impact information on Hombreol

• Here we show that the 3 alpha-reduced derivative of DHT, 5 alpha-androstane-3 alpha,17 beta-diol (5 alpha-adiol), is formed in testes of tammar wallaby pouch young and is higher in male than in female plasma in this species during early sexual differentiation [6].
• 3alpha-HSD catalyzes the inactivation of androgens in the prostate by converting 5alpha-dihydrotestosterone to 3alpha-androstanediol, where excess 5alpha-dihydrotestosterone is implicated in prostate disease [7].
• A similar complex can be detected when nuclei of vaginal cells are incubated with 3alpha,17beta-dihydroxy-5alpha-androstane, 3beta,17beta-dihydroxy-5alpha-androstane, and 3beta-hydroxy-androst-5-en-17-one which also have the capability of stimulating vaginal epithelium, although in somewhat different ways [8].
• These findings indicate that, in the prostate, type 2 3alpha-HSD does not interconvert 5alpha-DHT and 3alpha-androstanediol but inactivates 5alpha-DHT through its 3-ketosteroid reductase activity [9].
• In androgen target tissues, 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) may regulate occupancy of the androgen receptor (AR) by catalyzing the interconversion of 5alpha-dihydrotestosterone (5alpha-DHT) (a potent androgen) and 3alpha-androstanediol (a weak androgen) [9].

Chemical compound and disease context of Hombreol

• Mean serum 5alpha-androstane-3alpha,17beta-diol glucuronide (3alpha-AdiolG) levels in all three patient groups (6.50+/-4.10, 8.90+/-5.80, and 14.70+/-8.90 nmol/l, respectively) correlated with the grade of alopecia (I-III) and were significantly higher than in the control group (4.80+/-2.05 nmol/l, P < 0.005) [10].
• Increase in plasma 5 alpha-androstane-3 alpha,17 beta-diol glucuronide as a marker of peripheral androgen action in hirsutism: a side-effect induced by cyclosporine A [11].
• Testicular tissue obtained from ten patients orchiectomized for prostatic cancer was incubated with [3H]5 alpha-dihydrotestosterone (DHT) in order to study the metabolic transformation into 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol) and 5 alpha-androstane-3 beta,17 beta-diol (3 beta-diol) [12].

Biological context of Hombreol

• Results: In both cohorts, (TAAAA)(n) and rs1799941 genotypes were associated with serum levels of SHBG (P < 0.001), dihydrotestosterone (P < 0.05), and 5alpha-androstane-3alpha,17beta-diol glucuronides (P < 0.05) [13].
• AKR1C3 is also the dominant form in the uterus and is responsible for the synthesis of 3alpha-androstanediol which has been implicated as a parturition hormone [14].
• Changes in serum concentration and ovarian content of 5 alpha-androstane-3 alpha,17 beta-diol in the female rat approaching first ovulation [15].
• It is suggested that one form of cytochrome P-450 catalyzes the hydroxylation of 5alpha-androstane-3alpha,17beta-diol in the 2beta- and 18-positions, another form the 12beta-, 15alpha- and 16alpha-hydroxylations of the same substrate and a third form the 15beta-hydroxylation of 5alpha-androstane-3alpha,17beta-diol3,17-disulphate [16].
• However, 5alpha-androstan-3alpha,17beta-diol and 3alpha-hydroxy-5alpha-pregnan-20-one were shown to be neuroactive in mammals, modulating sexual behavior [17].

Anatomical context of Hombreol

• Metabolism of androsterone and 5 alpha-androstane-3 alpha,17 beta-diol in human lung tissue and in pulmonary endothelial cells in culture [18].
• Testosterone, 5 alpha-androstane-17 beta-ol-3-one (DHT) and 5 alpha-androstane-3 alpha,17 beta-diol (Adiol) concentrations were measured in postmortem tissues (pubic skin, scrotal skin, thigh skin, and striated muscle) from 24 males, aged 20-82 yr [19].
• Increased plasma 5 alpha-androstane-3 alpha,17 beta-diol glucuronide concentration in clinically euthyroid women with suppressed plasma thyrotropin levels: further evidence for generalized tissue overexposure to thyroid hormones in these subjects [20].
• Plasma levels of androstane-3alpha,17beta-diol glucuronide (3alpha-DIOL-G) and androsterone glucuronide (ADT-G) as well as testosterone and adrenal C19 steroid concentrations were measured in a sample of 80 men in whom visceral adipose tissue (AT) accumulation was also determined by computed tomography [21].
• Formation and secretion of 5alpha-androstan-17beta-ol-3-one, 5alpha-androstan-3alpha,17beta-diol and 5alpha-androstan-3beta,17beta-diol by the perfused rabbit testis epididymis [22].

Associations of Hombreol with other chemical compounds

• Testes were biopsied for estimation of intratesticular T, dihydrotestosterone, and 5alpha-androstane-3alpha,17beta-diol [23].
• In the tammar wallaby, Macropus eugenii, the testicular androgen 5 alpha-androstane-3 alpha,17 beta-diol (5 alpha-adiol) is formed in the developing testis, is secreted into plasma and has the capacity to virilize female young pouch when administered exogenously [24].
• Nine blood tests on both the first and eighth days allowed the measurement of DHEA, its sulfate DHEAS, and metabolites: testosterone, 5alpha-androstan-3alpha,17beta-diol glucuronide, estradiol, and estrone [25].
• In accordance with recent findings, no change in serum testosterone and significant decreases in 5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol glucosiduronate, and androsterone glucosiduronate levels were observed after treatment [26].
• The existence of 5alpha-androstane-3alpha,17beta-diol in the androstanediol fraction could be demonstrated by gas chromatography and mass spectrometry (GC-MS) [27].

Gene context of Hombreol

• RESULTS: AKR1C2 preferentially reduces DHT to the weak metabolite 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol) without conversion of 3 alpha-diol to DHT in the PC-3 cell line, and its expression was increased by DHT treatment in LNCaP cells [28].
• UGT2B4(E458) conjugates hyodeoxycholic acid (HDCA) as well as 4-hydroxyestrone (4-OH-E1), androstane-3alpha,17beta-diol (3alpha-diol) and androsterone (ADT) [29].
• A neuroactive steroid 5alpha-androstane-3alpha,17beta-diol regulates androgen receptor level in astrocytes [2].
• A human cDNA, UDPGTh-3, encoding a dihydrotestosterone/5 alpha-androstane-3 alpha,17 beta-diol UDP- glucuronosyltransferase (transferase) has been isolated and characterized [30].
• Under these conditions the effect of exposure to FGF-2 at doses ranging from 0.1-10 ng/ml was shown to cause a significant stimulation of basal, but not LH-stimulated, 5 alpha-androstane 3 alpha,17 beta-diol production over 24h in culture [31].

Analytical, diagnostic and therapeutic context of Hombreol

• Urinary 5 alpha-androstane-3 alpha,17 beta-diol radioimmunoassay: a new clinical evaluation [32].
• Main Outcome Measures: We measured serum levels of SHBG, testosterone, estradiol, dihydrotestosterone, 5alpha-androstane-3alpha,17beta-diol glucuronides, androsterone glucuronide, and BMD determined by dual-energy x-ray absorptiometry [13].
• The synthetic pathway by which 5alpha-androstane-3alpha,17beta-diol (5alpha-adiol) is formed in the testes of tammar wallaby pouch young was investigated by incubating testes from d 20-40 males with various radioactive precursors and analyzing the metabolites by thin-layer chromatography and HPLC [33].
• The efficacy of 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-Androstanediol; 3 alpha-Diol) and 4-pregnen-3,20-dione (progesterone; P) in promoting analgesia was investigated [34].
• The neurosteroid, 3alpha-androstanediol, prevents inhibitory avoidance deficits and pyknotic cells in the granule layer of the dentate gyrus induced by adrenalectomy in rats [35].

References