Disease relevance of ANDROSTANE-3,17-DIOL

• The induction of prostatic hypertrophy in the dog with androstanediol [1].
• Blood and urine specimens from 27 premenopausal breast cancer patients and 62 healthy controls have been compared with respect to concentration of testosterone and progesterone in blood and of testosterone and androstanediol in urine, measured in the luteal phase of the menstrual cycle [2].
• However, we have found that serum androstanediol glucuronide (3 alpha-diol G) is markedly increased in idiopathic hirsutism and it serves as an excellent marker of peripheral androgen metabolism and action [3].
• In intact pouch young studied between d 10 and 34, administration of the 5alpha-reductase inhibitor, 17beta-(N,N-diethyl)carbamoyl-4-methyl-4-aza-5alpha-androstan-3-one, blocked virilization of the Wolffian ducts in males, and administration of androstanediol caused virilization of the Wolffian ducts in females [4].
• Atrophy of the epithelium and stromal sclerosis were the salient features of antiandrogen-treated castrated animals, while hypertrophy or hyperplasia of both the epithelium and stroma was a major finding in androstanediol-substituted castrated animals [5].

High impact information on ANDROSTANE-3,17-DIOL

• The urine of 26 otherwise healthy women with fibrocystic disease of the breast was assayed by gas chromatography for testosterone and androstanediol (5alpha-androstane-3alpha, 17beta-diol), the major metabolite of dihydrotestosterone [6].
• Data are presented on the daily urinary excretion of androstanediol and testosterone in healthy adults using a sensitive radioligand assay [7].
• A radioimmunoassay using as antibody against testosterone-3-carboxymethyloxime-BSA is described for the measurement of androstanediol (5alpha-androstane-3alpha,17beta-diol) in human plasma [8].
• Purified Leydig cells from pubertal MIS-KO mice had lower testosterone but higher androstanediol and androstenedione production rates [9].
• Using androstanediol (Adiol) as a substrate, enzyme kinetics were linear with respect to time and enzyme concentration [10].

Chemical compound and disease context of ANDROSTANE-3,17-DIOL

• Approximately half the animals receiving androstanediol alone and all of those receiving androstanediol plus estradiol fulfill the weight and histological criteria for prostatic hypertrophy in the dog [1].
• We therefore conclude that the stroma is the main site for the transformation of dihydrotestosterone to the androstanediol epimers and that the asymmetric distribution of the 3 alpha (beta)-hydroxysteroid dehydrogenase may be instrumental in the development of hyperplasia in the prostate gland [11].
• Preliminary reports of androstanediol glucuronide indicated that it was a peripherally-derived androgen and had a high correlation with clinical gradings of hirsutism [12].

Biological context of ANDROSTANE-3,17-DIOL

• Androstanediol treatment disrupted spermatogenesis in most tubules [13].
• Sperm motility decreased within 40 days and by Day 70 non-motile spermatozoa were seen in 2 animals of each group treated with androstanediol [13].

Anatomical context of ANDROSTANE-3,17-DIOL

• Effect of antibodies to estrogen receptor on the binding of 3H-labeled antiestrogens and androstanediol in the uterus [14].
• General squamous metaplasia of the epithelium and regressive alterations of stromal cells were most obvious in animals treated with estradiol plus androstanediol [5].
• In both fractions, the amount of 5 alpha-DHT was greater than that of androstanediol while the reverse was true for the mitochondria and microsomes [15].
• Formation of androstanediol was normal in testes from mice deficient in steroid 5alpha-reductase 2 but absent in testes from mice deficient in steroid 5alpha-reductase 1, indicating that isoenzyme 2 is not expressed in day 24-26 testes [16].
• Of these substrates, only androstanediol exhibited nontraditional kinetics using human liver microsomes [17].

Associations of ANDROSTANE-3,17-DIOL with other chemical compounds

• These results confirm that ER directly binds androstanediol, tamoxifen, and hydroxytamoxifen [14].
• Seven urinary androgen metabolites, including androstanediol (5 alpha-androstan-3 alpha-17 beta-diol and 5 beta-androstan-3 alpha-17 beta-diol), were identified in glucoronidase-hydrolyzed, ether-extracted Eld's deer urine pools after gas chromatography/mass spectrometry [18].
• Model-fitting analysis suggested that fasting insulin level, androstanediol glucuronide, and body mass index (BMI) were significantly influenced by genetic factors [19].
• Kidney microsomes showed a Km of 19.4 and 26.9 microM, respectively, for androstanediol and androsterone [20].
• Plasma total testosterone (T), non-SHBG bound T, androstenedione (A), dehydroepiandrosterone sulphate (DHEAS), androstanediol glucuronide (3 alpha-diol G) and sex hormone binding globulin (SHBG) levels were measured before and every 3 months during therapy, on day 5 of the cycle [21].

Gene context of ANDROSTANE-3,17-DIOL

• In this study, testosterone, dihydrotestosterone (DHT), 3 alpha androstanediol (3 alpha diol), IGF-I, IGF-II, IGFBP2, and IGFBP3 concentrations were evaluated in human benign prostatic hyperplasia (BPH) tissue [22].
• The Michaelis-Menten constant (Km) for UDPGT in liver microsomes was 20.4, 12.2, and 2.2 microM, respectively, for testosterone, androstanediol, and androsterone [20].
• Androgens in the serum and testes displayed an age-related alternating pattern with androstanediol being the major androgen produced at 27 days of age [23].
• Competition studies led us to believe that the binding of dihydrotesterone (DHT) was due to 3 alpha-hydroxysteroid dehydrogenase (3 alpha-OHSD) enzyme responsible for the conversion of DHT to androstanediol (Adiol) [24].
• An estrogen stimulated increase in prostatic androgen receptor content has been postulated as the mechanism by which canine prostatic hyperplasia can be induced in the castrate dog treated with androstanediol and estradiol but not by androstanediol alone [25].

Analytical, diagnostic and therapeutic context of ANDROSTANE-3,17-DIOL

• To chart the pattern of androstanediol formation in another marsupial species, the testes or fragments of testes from brushtail possums (Trichosurus vulpecula) that spanned the age range from early pouch young to mature adults were incubated with (3)H-progesterone and the products were identified by high-performance liquid chromatography [26].

References