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Reproductive Sciences (Thousand Oaks,... Jul 2017Proliferation in endometria of women with polycystic ovarian syndrome (PCOS) is increased, similar to the biosynthesis of androstenediol (estrogenic metabolite). As...
Proliferation in endometria of women with polycystic ovarian syndrome (PCOS) is increased, similar to the biosynthesis of androstenediol (estrogenic metabolite). As previously shown, in human endometrial cells, androstenediol increases CYCLIN D1 levels and KI67 and decreases P27 content. The objective of the present investigation was to determine the mechanisms by which androstenediol promotes endometrial cell-cycle progression. Estrogen receptor α (ERα) activation and changes in CYCLIN D1 and P27 levels were evaluated by Western blot in T-HESC and St-T1b endometrial cell lines, using receptor antagonists; activation of PI3K-protein kinase B (AKT) and mitogen-activated protein kinases-extracellular signal-regulated kinases (MAPK-ERK)1/2 pathways was evaluated using PI3K, MAPK/ERK kinase (MEK)1/2, and RNA-polymerase II inhibitors. The data showed that androstenediol treatment significantly increases CYCLIN D1 and decreases P27 levels through ERα activation ( P < .05). In addition, an increase in AKT/ERK1/2 phosphorylations was determined ( P < .05). In the presence of RNA-polymerase II inhibitor, phosphorylation of AKT/ERK1/2 decreased ( P < .05), meaning that endometrial cells need transcriptional activity to activate the kinases involved. It was also observed that PI3K action is required for P27 and CYCLIN D1 changes. Therefore, the action of androstenediol in endometria depends on PI3K-AKT and MAPK-ERK1/2 pathways activation, together with cell transcriptional machinery. This could be of clinical significance, as in pathologies such as PCOS, increased endometrial levels of androstenediol together with a high prevalence of endometrial hyperplasia and adenocarcinoma have been reported.
Topics: Androstenediol; Butadienes; Cell Proliferation; Chromones; Endometrium; Enzyme Inhibitors; Estradiol; Extracellular Signal-Regulated MAP Kinases; Female; Humans; Morpholines; Nitriles; Phosphoinositide-3 Kinase Inhibitors; Phosphorylation; Signal Transduction; Stromal Cells; Testosterone
PubMed: 27879454
DOI: 10.1177/1933719116678689 -
Archives of Virology 1992We previously reported that subcutaneous injection of DHEA (5-androsten-3 beta-ol-17-one, dehydroepiandrosterone) protected mice from lethal infection. This included...
We previously reported that subcutaneous injection of DHEA (5-androsten-3 beta-ol-17-one, dehydroepiandrosterone) protected mice from lethal infection. This included both a lethal herpes virus type 2 encephalitis and a lethal systemic coxsackievirus B4 (CB4) infection. Androstenediol (5-androsten-3 beta-17 beta-diol, AED), a metabolic product of DHEA is up to 100 x more effective in regulating systemic resistance against lethal infection with CB 4 than its precursor DHEA. Compared to DHEA, treatment with AED was markedly superior in protecting mice against virus induced myocardiopathy, pancreopathy, and mortality. In addition to its protective effect, AED but not DHEA, induced a 3-4 fold proliferation of the spleen and thymus in virus infected animals; this effect of AED was only seen above a certain threshold dose. Neither steroid, however, has shown any significant direct antiviral effect in vitro; similarly, virus tissues titers in vivo are not affected by the hormones. Additionally, both DHEA and AED protected against a lethal infection with Enterococcus faecalis. These observations demonstrate that the steroid hormones DHEA and AED provide a novel approach for prevention and protection of the host from a variety of infectious diseases.
Topics: Androstenediols; Animals; Antiviral Agents; Dehydroepiandrosterone; Enterovirus Infections; Gram-Positive Bacterial Infections; HeLa Cells; Humans; Immunity, Innate; Mice; Organ Size; Spleen; Vero Cells; Virus Replication
PubMed: 1456887
DOI: 10.1007/BF01309578 -
Bioorganic & Medicinal Chemistry Letters Feb 2006A series of 19-substituted androstenediol derivatives was prepared. Some of the novel analogs were surprisingly potent and selective ligands for ER-beta.
A series of 19-substituted androstenediol derivatives was prepared. Some of the novel analogs were surprisingly potent and selective ligands for ER-beta.
Topics: Androstenediol; Crystallography, X-Ray; Estrogen Receptor beta; Humans; Ligands; Models, Molecular; Molecular Conformation; Selective Estrogen Receptor Modulators; Stereoisomerism; Structure-Activity Relationship
PubMed: 16309907
DOI: 10.1016/j.bmcl.2005.11.014 -
Frontiers in Cellular Neuroscience 2017: We have previously shown that the neurosteroid androstenediol (ADIOL) promotes remyelination following gliotoxin-induced demyelination. However, the impact of this...
: We have previously shown that the neurosteroid androstenediol (ADIOL) promotes remyelination following gliotoxin-induced demyelination. However, the impact of this ADIOL on axonal recovery is not yet known. In the present study, we investigated the impact of ADIOL on axonal integrity following a focal demyelination in the corpus callosum. : A 2 μl solution of either ethidium bromide (EB; 0.04%) or pyrogen-free saline were stereotaxically injected into the corpus callosum of Sprague Dawley rats. Each of these two rat groups was divided into two subgroups and received daily subcutaneous injections of either ADIOL (5 mg/kg) or vehicle. The brains were collected at 2, 7 and 14 days post-stereotaxic injection. Immunofluorescent staining was used to explore the impact of ADIOL on axonal integrity (neurofilament (NF)-M) and microglial activation (ionized calcium binding adapter molecule 1, Iba1). The inducible nitric oxide synthase (iNOS) and arginase-1 (arg-1), two major markers of microglial polarization towards the proinflammatory M1 and the regulatory M2 phenotypes respectively, were monitored using western blot. : ADIOL increased the density of NF fibers and decreased the extent of axonal damage in the vicinity of the demyelination lesion. ADIOL-induced decrease in axonal damage was manifested by decreased number of axonal spheroids at both 2 and 7 days post-demyelination insult. This reduced axonopathy was associated with decreased expression of iNOS and enhanced expression of arg-1 during the acute phase. : These data strongly suggest that ADIOL reduces demyelination-induced axonal damage, likely by dampening the local inflammatory response in the white matter and shifting microglial polarization towards a reparative mode.
PubMed: 28280460
DOI: 10.3389/fncel.2017.00049 -
Bioorganic & Medicinal Chemistry Letters May 2007A series of bridged androstenediol derivatives was prepared. The bridged compounds exhibited reduced ER-beta selectivity relative to uncyclized analogs.
A series of bridged androstenediol derivatives was prepared. The bridged compounds exhibited reduced ER-beta selectivity relative to uncyclized analogs.
Topics: Androstenediols; Cyclization; Estrogen Receptor beta; Humans; Models, Molecular; Molecular Structure; Selective Estrogen Receptor Modulators; Structure-Activity Relationship
PubMed: 17448656
DOI: 10.1016/j.bmcl.2006.12.053 -
The Journal of Clinical Endocrinology... Dec 1972
Topics: Acetylation; Adult; Androstanes; Binding, Competitive; Carbon Isotopes; Chromatography; Chromatography, Paper; Crystallization; Female; Humans; Male; Methods; Sex Factors; Tritium; gamma-Globulins
PubMed: 4117700
DOI: 10.1210/jcem-35-6-818 -
Cytokine Apr 2006Although administration of androstenediol (a metabolite of dehydroepiandrosterone) following trauma-hemorrhage (T-H) produces beneficial effects on inflammatory...
Although administration of androstenediol (a metabolite of dehydroepiandrosterone) following trauma-hemorrhage (T-H) produces beneficial effects on inflammatory cytokines and organ function, it remains unknown whether this metabolite has any salutary effects in preventing alterations in immune cell cytokine production following a combined insult of T-H and sepsis. To examine this, male rats underwent laparotomy, hemorrhagic shock (mean BP 40 mmHg for 90 min) and resuscitation or sham operation. Androstenediol (1 mg/kg BW i.v.) or vehicle was administered at the end of resuscitation. Twenty hrs after T-H or sham operation, sepsis was induced by cecal ligation and puncture (CLP). Five hours thereafter, plasma cytokine levels and cytokine production of various immune cells were determined. In a separate set of experiments, survival was monitored for 10 days after the induction of sepsis. Administration of androstenediol markedly decreased plasma IL-6 and TNF-alpha levels following T-H and CLP. Furthermore, it prevented the increased production of IL-6 and TNF-alpha by Kupffer cells and alveolar macrophages and attenuated the decrease in IL-6 and TNF-alpha production by splenic macrophages; however, it had no significant effects on the depressed IL-6 and TNF-alpha production by PBMC following T-H and CLP. The depressed IL-2 and IFN-gamma production by splenocytes under those conditions was attenuated by the administration of androstenediol. Furthermore, survival rate following T-H and subsequent sepsis was improved by androstenediol treatment. Since androstenediol administration following T-H attenuated cytokine production and reduced mortality in a double-hit model of T-H and sepsis, this agent appears to be a novel and useful adjunct for maintaining the immune cell functions following T-H and for decreasing the mortality rate from subsequent susceptibility to sepsis.
Topics: Anabolic Agents; Androstenediol; Animals; Autoimmunity; Cytokines; Female; Hemorrhage; Interleukin-10; Leukocytes, Mononuclear; Male; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, Transgenic; Sepsis
PubMed: 16737821
DOI: 10.1016/j.cyto.2006.04.007 -
Menopause (New York, N.Y.) Jun 2012The perimenopausal increase in circulating dehydroepiandrosterone sulfate (DHEAS) levels during the menopausal transition (MT) is accompanied by other adrenal steroids...
OBJECTIVE
The perimenopausal increase in circulating dehydroepiandrosterone sulfate (DHEAS) levels during the menopausal transition (MT) is accompanied by other adrenal steroids that have the potential to alter estrogen/androgen balance and explain the wide interwoman range of estrogen-related symptoms experienced during the MT.
METHODS
Annual serum samples from the Study of Women's Health Across the Nation, which had previously been analyzed for immunoreactive estradiol (E2), testosterone, DHEAS, and sex hormone-binding globulin, were selected based on DHEAS concentration and analyzed for immunoreactive and bioactive estrogens and androgens, including immunoreactive androstenedione, dehydroepiandrosterone, and 5-androstene-3β,17β-diol (androstenediol [Adiol]).
RESULTS
A two-fold increase in circulating androstenedione and testosterone was found to rise in parallel with the rise in circulating DHEAS, whereas dehydroepiandrosterone and Adiol concentrations rose seven- to eight-fold. Circulating Adiol, which has both androgenic and estrogenic biological activity, was significantly associated (P < 0.02) with circulating estrogen bioactivity only when E2 concentrations were low and Adiol levels were high.
CONCLUSIONS
The wide range of circulating levels of Adiol and its contribution to total circulating estrogenicity during the MT is consistent with the observed interwoman difference in symptoms at this time. Therefore, we conclude that Adiol contributes to circulating estrogenicity when E2 production falls at menopause and may contribute significantly to the endocrine changes experienced by midlife women.
Topics: Adult; Androstenediol; Androstenedione; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estradiol; Female; Humans; Middle Aged; Perimenopause; Testosterone
PubMed: 22415563
DOI: 10.1097/gme.0b013e31823df577 -
Bulletin de La Federation Des Societes... 1954
Topics: Androgens; Androstenediol; Female; Genital Diseases, Female; Humans
PubMed: 13182367
DOI: No ID Found -
Brain, Behavior, and Immunity Nov 2006Restraint stress (RST) delays wound closure and suppresses pro-inflammatory gene expression by a glucocorticoid-dependent mechanism. Because androstenediol (AED)... (Comparative Study)
Comparative Study
Restraint stress (RST) delays wound closure and suppresses pro-inflammatory gene expression by a glucocorticoid-dependent mechanism. Because androstenediol (AED) ameliorates many of the anti-inflammatory influences of glucocorticoids (GC) in vitro, it was hypothesized that treatment of stressed animals with AED would ameliorate the suppressive influence of restraint and restore healing to control levels. To test this hypothesis, male CD1 mice were subjected to nightly cycles of RST beginning 3 days prior to placement of two 3.5 mm full-thickness cutaneous wounds. To assess the influence of AED treatment on wound repair, mice were injected subcutaneously with 2.0 mg of AED or an equivalent volume of delivery vehicle (VEH) prior to wounding. The rate of wound closure was assessed daily by photoplanimetry. In addition, at 3, 6, 12, and 24 h post wounding, IL-1beta, MCP-1, and PDGF RNAs were quantified in wounds as a measure of inflammatory gene expression. The data showed that RST significantly delayed closure as compared to controls. In parallel, RST significantly decreased IL-1beta and PDGF gene expression as early as 12 h after wounding. In contrast, treatment with AED prevented the stress-induced delay in healing. Whereas wounds on VEH/RST mice did not achieve 50% closure until day 7, wounds on AED-treated animals, whether subjected to RST or not, had closed by 50% within 3 days of wounding. In addition, AED treatment prevented the stress-induced suppression of IL-1beta and PDGF gene expression 24 h after injury. Therefore, AED may provide a pharmacologic approach to ameliorate the anti-inflammatory effects of behavioral stress and in doing so, may improve tissue repair.
Topics: Androstenediol; Animals; Chemokine CCL2; Gene Expression Regulation; Interleukin-1beta; Male; Mice; Platelet-Derived Growth Factor; RNA; Restraint, Physical; Skin; Wound Healing
PubMed: 16730942
DOI: 10.1016/j.bbi.2006.03.007