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Endocrinologia Japonica Jun 1966
Topics: Androgens; Animals; Carbon Isotopes; Chorionic Gonadotropin; Chromatography, Gas; Chromatography, Paper; Dehydroepiandrosterone; Humans; Hypophysectomy; Male; Rats; Spectrum Analysis; Testis; Testosterone
PubMed: 4225645
DOI: 10.1507/endocrj1954.13.160 -
The Journal of Steroid Biochemistry and... Dec 2002Several precursors of testosterone and nandrolone introduced on the nutritional supplement market as performance enhancing drugs are banned in sports. Until now they are...
Several precursors of testosterone and nandrolone introduced on the nutritional supplement market as performance enhancing drugs are banned in sports. Until now they are legally sold without a prescription in the US. Results of excretion studies with related compounds including 7-keto-DHEA and 1-androstenediol are presented. The main metabolites of 7-keto-DHEA are 7-hydroxylated compounds. The commercial 1-androstenediol preparation was contaminated with several other anabolic steroids. Oxidation of 1-androstenediol to 1-androstenedione seems to be the major renal metabolic pathway. Additionally contaminated nutritional supplements containing banned substances not indicated on the label were administered. The results of the excretion studies indicate that after the intake of amounts substantially lower than the recommended dose athletes can fail a doping test for periods up to 120 h.
Topics: Adult; Dehydroepiandrosterone; Dietary Supplements; Doping in Sports; Estranes; Hormones; Humans; Male; Mass Spectrometry; Middle Aged; Physical Endurance; Sports; Substance Abuse Detection; Time Factors
PubMed: 12650722
DOI: 10.1016/s0960-0760(02)00274-1 -
Journal of Applied Physiology... Mar 2007Soft tissue trauma and hemorrhage (T-H) diminishes various aspects of liver function, while it increases hepatic nitrate/nitrite, inducible nitric oxide synthase (iNOS),...
Soft tissue trauma and hemorrhage (T-H) diminishes various aspects of liver function, while it increases hepatic nitrate/nitrite, inducible nitric oxide synthase (iNOS), and endothelin-1 levels. Treatment with androstenediol (AED) inhibits the T-H-induced alterations of the above parameters. We sought to identify the molecular events underlying the beneficial effect of AED. Exposure of rats to T-H significantly increased the caspase-3 activity and protein, whereas treatment with AED significantly limited these increases. AED treatment also suppressed the T-H-induced increase in iNOS by effectively altering the levels of key transcription factors involved in the regulation of iNOS expression. Immunoprecipitation and immunoblotting analyses indicate that T-H increased apoptosome formation, and AED treatment significantly decreased it. Modulating the iNOS protein by transfecting cells with iNOS gene or small interfering RNA further confirmed the correlation between iNOS and caspase-3. Our data indicate that AED limits caspase-3 expression by suppressing the expression of transcription factors involved in the production of iNOS, resulting in decreased apoptosome. AED can potentially be a useful adjuvant for limiting liver apoptosis following T-H shock.
Topics: Androstenediol; Animals; Apoptosis; Caspase 3; Down-Regulation; Liver; Male; NF-kappa B; Nitric Oxide Synthase Type II; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Shock, Hemorrhagic; Tumor Suppressor Protein p53; Wounds and Injuries
PubMed: 17110508
DOI: 10.1152/japplphysiol.00919.2006 -
Annals of the New York Academy of... 2000Androstenetriol (AET) and Androstenediol (AED) upregulate host immunity, leading to increased resistance against infections. AET augments IL-2, IL-3, IFN gamma levels,...
Androstenetriol (AET) and Androstenediol (AED) upregulate host immunity, leading to increased resistance against infections. AET augments IL-2, IL-3, IFN gamma levels, and counteracts hydrocortisone immune suppression. AET and AED at a dose of 0.75 mg/- and 8.0 mg/25-g mouse, protected 60 and 70%, respectively, of C57/BL/6J mice irradiated with a lethal dose. These hormones also protected mice irradiated with 6 Gy and infected with a coxsackievirus B4 LD50. AET significantly increased spleen lymphocyte numbers at 7, 14, and 21 days after a 6-Gy exposure. Fluorescent activated cell-sorter analysis of irradiated mice, spleen, and bone marrow showed that AET significantly augmented the myeloid precursor markers, CD11b/Mac-1, and B220 (pan B), as well as the absolute numbers of CD4+/CD8+ cells over the 21 days of testing. Overall, the data are consistent with AET/AED inducing a more rapid recovery of all hematopoietic precursors from the small number of surviving stem cells.
Topics: Anabolic Agents; Androstenediol; Animals; Immunity; Male; Mice; Mice, Inbred C57BL; Neuroimmunomodulation; Radiation Injuries
PubMed: 11268417
DOI: 10.1111/j.1749-6632.2000.tb05452.x -
Journal of Applied Physiology... Jan 2002The effectiveness of orally ingested androstenediol in raising serum testosterone concentrations may be limited because of hepatic breakdown of the ingested androgens.... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The effectiveness of orally ingested androstenediol in raising serum testosterone concentrations may be limited because of hepatic breakdown of the ingested androgens. Because androstenediol administered sublingually with cyclodextrin bypasses first-pass hepatic catabolism, we evaluated the acute hormonal response to sublingual cyclodextrin androstenediol supplement in young men. Eight men (22.9 +/- 1.2 yr) experienced in strength training consumed either 20 mg androstenediol in a sublingual cyclodextrin tablet (Sl Diol) or placebo (Pl) separated by at least 1 wk in a randomized, double-blind, crossover manner. Blood samples were collected before supplementation and at 30-min intervals for 3 h after supplementation. Serum hormone concentrations did not change with Pl. Serum androstenedione concentrations were increased (P < 0.05) above baseline (11.2 +/- 1.1 nmol/l) with Sl Diol from 60 to 180 min after intake and reached a peak concentration of 25.2 +/- 2.9 nmol/l at 120 min. Serum free testosterone concentrations were increased from 86.2 +/- 9.1 pmol/l with Sl Diol from 30 to 180 min and reached a peak concentration of 175.4 +/- 12.2 pmol/l at 60 min. Serum total testosterone concentrations increased above basal (25.6 +/- 2.3 nmol/l) from 30 to 180 min with Sl Diol and reached a peak concentration of 47.9 + 2.9 nmol/l at 60 min. Serum estradiol concentrations were elevated (P < 0.05) above baseline (0.08 +/- 0.01 nmol/l) from 30 to 180 min with Sl Diol and reached 0.14 +/- 0.02 nmol/l at 180 min. These data indicate that sublingual cyclodextrin androstenediol intake increases serum androstenedione, free testosterone, total testosterone, and estradiol concentrations.
Topics: Administration, Sublingual; Adult; Androstenediol; Body Composition; Cyclodextrins; Diet; Estradiol; Excipients; Hormones; Humans; Male; Testosterone; Weight Lifting
PubMed: 11744653
DOI: 10.1152/jappl.2002.92.1.142 -
Radiation Research Sep 2001We showed previously that 5-androstenediol stimulates myelopoiesis, increases the numbers of circulating neutrophils and platelets, and enhances resistance to infection...
We showed previously that 5-androstenediol stimulates myelopoiesis, increases the numbers of circulating neutrophils and platelets, and enhances resistance to infection in gamma-irradiated mice. We have extended those studies to include monocytes, natural killer (NK) cells, eosinophils and basophils, and we have measured the activation marker CD11b using flow cytometry. Androstenediol (160 mg/kg) was administered subcutaneously to female B6D2F1 mice 24 h before whole-body gamma irradiation. Androstenediol treatments increased the blood levels of neutrophils, monocytes and NK cells in unirradiated animals; decreased the numbers of circulating eosinophils; and ameliorated radiation-induced decreases in neutrophils, monocytes, NK cells, erythrocytes and platelets. The androstenediol treatments had no significant effect on the numbers of circulating B cells or T cells. CD11b labeling intensity on monocytes was decreased slightly after androstenediol treatment. In contrast, radiation or androstenediol alone caused increases in CD11b labeling intensity on NK cells. Androstenediol and radiation combined caused a marked increase in NK cell CD11b. The results indicate that androstenediol increases the numbers of the three major cell types of the innate immune system (neutrophils, monocytes and NK cells), that androstenediol-induced changes in blood elements in irradiated animals persist for at least several weeks, and that there is a significant positive interaction between radiation and administration of androstenediol in the activation of NK cells.
Topics: Androstenediol; Animals; Erythrocyte Count; Female; Flow Cytometry; Leukocyte Count; Macrophage-1 Antigen; Mice; Neutrophils; Peroxidases; Radiation-Protective Agents; Whole-Body Irradiation
PubMed: 11500137
DOI: 10.1667/0033-7587(2001)156[0283:ivrbas]2.0.co;2 -
British Journal of Cancer Apr 2009Androst-5-ene-3beta, 17beta-diol (AED) is an adrenal hormone that has been reported to sustain prostate cancer growth after androgen deprivation therapy (ADT). LNCaP...
Androst-5-ene-3beta, 17beta-diol (AED) is an adrenal hormone that has been reported to sustain prostate cancer growth after androgen deprivation therapy (ADT). LNCaP cells express a mutated androgen receptor that confers the ability to respond not only to androgen but also to oestrogen and adrenal hormones such as AED, and thus provide a cell line useful for identifying compounds capable of inhibiting AED-stimulated cell growth. We sought to determine whether structurally related steroids could inhibit AED-stimulated LNCaP cell growth in vitro and tumour growth in vivo. We report here the identification of a novel androstane steroid, HE3235 (17alpha-ethynyl-5alpha-androstan-3alpha, 17beta-diol), with significant inhibitory activity for AED-stimulated LNCaP proliferation. This inhibitory activity is accompanied by an increase in the number of apoptotic cells. Animal studies have confirmed the cytoreductive activity of HE3235 on LNCaP tumours. The results suggest that this compound may be of clinical use in castration-resistant prostate cancer.
Topics: Androstanols; Androstenediol; Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Humans; Male; Mice; Mice, SCID; Prostatic Neoplasms; Receptors, Androgen
PubMed: 19337256
DOI: 10.1038/sj.bjc.6604987 -
Endocrine Research Aug 2019: It has been proposed that DHEA influences bone formation through, bioconversion to 17β-estradiol; however, DHEA is converted to Δ5-androstenediol (Δ5-Adiol), a...
The Non-Aromatic Δ5-Androstenediol Derivative of Dehydroepiandrosterone Acts as an Estrogen Agonist in Neonatal Rat Osteoblasts through an Estrogen Receptor α-related Mechanism.
: It has been proposed that DHEA influences bone formation through, bioconversion to 17β-estradiol; however, DHEA is converted to Δ5-androstenediol (Δ5-Adiol), a metabolite with estrogenic potential involved in diverse biological process. To gain new insight into the role of Δ5-Adiol in bone cells, we examined DHEA and Δ5-Adiol effects in neonatal rat and human hFOB1.19 osteoblasts. : Osteoblast activity was assessed by analyzing proliferation, alkaline phosphatase activity, and expression of and . We also examined binding affinities for osteoblast-ER and transcriptional activation of human (h)ERα, hERβ or hAR in U2-OS cells. : The most striking finding was that Δ5-Adiol had greater stimulatory effect than DHEA on rat osteoblast proliferation and differentiation, as well as expression in human osteoblasts. Interestingly, the Δ5-Adiol or DHEA-induced effects were not precluded with letrozole or trilostane, consistent with bioconversion of DHEA to Δ5-Adiol due to elevated expression of in neonatal rat osteoblasts, suggesting a high level of 17β-hydroxysteroid dehydrogenase type 1 activity. Conversely, Δ5-Adiol and DHEA-induced proliferative effects were inhibited with ICI 182780 alone or combined with trilostane, which correlates with the higher binding affinity of Δ5-Adiol for ER compared to DHEA. Furthermore, Δ5-Adiol showed a greater relative agonist activity for hERα than for hERβ or hAR. : This study is the first to show that a bioactive DHEA derivative stimulates E-dependent osteoblast activities, including proliferation and differentiation in rat and human osteoblasts, through ERα-related mechanisms.
Topics: 17-Hydroxysteroid Dehydrogenases; Alkaline Phosphatase; Androstenediol; Animals; Cell Differentiation; Cell Proliferation; Dehydroepiandrosterone; Estrogen Receptor alpha; Female; Humans; Osteoblasts; Rats; Rats, Wistar
PubMed: 30580653
DOI: 10.1080/07435800.2018.1559185 -
Journal of Tropical Pediatrics Jun 2003In order to assess the effects of age-related changes of serum dehydroepiandrosterone sulphate (DHEAS) and androstenediol (AED) concentrations on BCG vaccination... (Comparative Study)
Comparative Study
In order to assess the effects of age-related changes of serum dehydroepiandrosterone sulphate (DHEAS) and androstenediol (AED) concentrations on BCG vaccination throughout the puberty period, we matched 41 prepubertal (mean age 8.63 +/- 1.36 years, range 8-14 years) and 43 pubertal (mean age 13.8 +/- 1.31 years, range 10-16 years) schoolchildren who were PPD negative and free of disease or medication known to affect immune function. The tuberculin test was performed 8 weeks after vaccination and tuberculin response and hormone levels were compared between prepubertal and pubertal subjects. We found a higher tuberculin response in the pubertal group when compared with the prepubertal ones. The pubertal children had 79.1 per cent tuberculin positivity compared with 46.4 per cent of prepubertal children (p < 0.05). Diameters of induration of the tuberculin test among prepubertal students vs. pubertal students were 9.5 +/- 3.8 mm and 11.9 +/- 3.7 mm, respectively (p < 0.005). Pubertal stage, testis volume, and pubic stage were also found to have significant effects on tuberculin test results. No difference was observed between both sexes with regard to responses of the tuberculin test in either the prepubertal or the pubertal group (p > 0.05). DHEAS and AED levels in the tuberculin-positive subjects were found to be significantly higher than tuberculin-negative ones (p = 0.040 and p = 0.046, respectively). Among both these hormones, only AED levels were correlated with tuberculin test responses. These results suggest that AED may play a role in the immunity to BCG vaccination and further immunological investigations are warranted to provide support for this idea.
Topics: Adjuvants, Immunologic; Adolescent; Aging; Androstenediol; BCG Vaccine; Child; Dehydroepiandrosterone Sulfate; Female; Humans; Male; Puberty; Tuberculin Test; Tuberculosis
PubMed: 12848211
DOI: 10.1093/tropej/49.3.181 -
Annals of Surgery Jul 2006To examine the mechanism by which androstenediol improves cardiac function following trauma-hemorrhage (T-H).
OBJECTIVE
To examine the mechanism by which androstenediol improves cardiac function following trauma-hemorrhage (T-H).
SUMMARY BACKGROUND DATA
Androstenediol administration improves cardiovascular function and attenuates proinflammatory cytokine production following T-H. Activation of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been shown to be protective following ischemic conditions. We hypothesized that PPAR-gamma activation plays a role in the androstenediol-mediated salutary effects on cardiac function following T-H.
METHODS
Male rats underwent laparotomy and hemorrhagic shock (40 mm Hg for 90 minutes), followed by resuscitation with 4 times the shed blood volume in the form of Ringer's lactate. Androstenediol (1 mg/kg body weight, i.v.) was administrated at the end of resuscitation. In a separate group of animals, a PPAR-gamma antagonist (GW9662) was administered simultaneously with androstenediol and animals were killed at 5 hours thereafter.
RESULTS
A decrease in cardiac function and an increase in IL-6 and iNOS gene expression were observed following T-H. Androstenediol treatment normalized cardiac function, increased PPAR-gamma DNA binding activity, attenuated IL-6 and iNOS gene expressions, and reduced plasma IL-6. Plasma 15-deoxy-Delta12, 14-prostaglandin J2 (PGJ2, an endogenous PPAR-gamma agonist) levels were also increased in androstenediol-treated T-H rats, but these levels were lower than those observed in shams. Coadministration of PPAR-gamma antagonist along with androstenediol, however, prevented the androstenediol-mediated reduction in cardiac iNOS and IL-6 expressions and abolished the improvements in cardiac function.
CONCLUSION
The androstenediol-mediated salutary effects on cardiac function following T-H appear to be mediated at least in part via PPAR-gamma activation, which down-regulates IL-6 and iNOS gene expression in the heart.
Topics: Anabolic Agents; Androstenediol; Anilides; Animals; Blotting, Western; Cardiac Output; Electrophoretic Mobility Shift Assay; Gene Expression; Interleukin-6; Male; Myocardium; Nitric Oxide Synthase Type II; PPAR gamma; Prostaglandin D2; Rats; Rats, Sprague-Dawley; Shock, Hemorrhagic; Ventricular Function, Left
PubMed: 16794398
DOI: 10.1097/01.sla.0000217709.00863.82