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Drug Discovery Today Feb 2024Moderate-to-high doses of ionizing irradiation can lead to potentially life-threatening morbidities and increase mortality risk. In preclinical testing, 5-androstenediol... (Review)
Review
Moderate-to-high doses of ionizing irradiation can lead to potentially life-threatening morbidities and increase mortality risk. In preclinical testing, 5-androstenediol has been shown to be effective in protecting against hematopoietic acute radiation syndrome. This agent is important for innate immunity, serves to modulate cell cycle progression, reduces radiation-induced apoptosis, and regulates DNA repair. The drug has been evaluated clinically for its pharmacokinetics and safety. The United States Food and Drug Administration granted investigational new drug status to its injectable depot formulation (NEUMUNE). Its safety and efficacy profiles make it an attractive candidate for further development as a radiation countermeasure.
Topics: United States; Humans; Acute Radiation Syndrome; Radiation-Protective Agents; Androstenediol; Immunity, Innate
PubMed: 38097137
DOI: 10.1016/j.drudis.2023.103856 -
Annals of the New York Academy of... Jul 2012Δ5-androstene-3β,17α-diol (17α-AED) mediates oncophagy of human myeloid, glioma, and breast tumor cells by apoptotic- and autophagic-programmed cell death pathways,... (Review)
Review
Δ5-androstene-3β,17α-diol (17α-AED) mediates oncophagy of human myeloid, glioma, and breast tumor cells by apoptotic- and autophagic-programmed cell death pathways, whereas the 17β-epimer does not. In hematologically derived myeloid tumor cells, 17α-AED induced apoptosis, as determined by TUNEL staining, caspase, PARP activation, and electron microscopy. In contrast, 17α-AED treatment of glioma cells of neuroectodermal lineaged induced autophagy, evident by the presence of acidic vesicular organelles, LC3 processing, and upregulation of beclin-1. Proliferation inhibition studies on primary and established glioma cells demonstrated that the IC-50 of the steroid is ∼15 μM. In the case of breast cancer cells, the bioactivity of 17α-AED is independent of the expression of estrogen or androgen receptors. Collectively, oncophagy is induced by 17α-AED treatment in human tumor cells and proceeds by the induction of either autophagy or apoptosis. The neoplastic cell determines which oncophagic pathway is utilized.
Topics: Androstenediol; Antineoplastic Agents, Hormonal; Apoptosis; Autophagy; Cell Line, Tumor; Cell Proliferation; Female; Humans; Neoplasms; Stereoisomerism; Structure-Activity Relationship
PubMed: 22823444
DOI: 10.1111/j.1749-6632.2012.06602.x -
American Journal of Men's Health Nov 2016An increasing number of men are being diagnosed with hypogonadism. While many benefit from testosterone supplementation therapy, others who do not meet the criteria for... (Review)
Review
An increasing number of men are being diagnosed with hypogonadism. While many benefit from testosterone supplementation therapy, others who do not meet the criteria for hormone supplementation have turned to dietary adjuncts as a way or gaining improvements in libido, energy, and physical performance. These oral adjunct medications include controlled substances such as androstenedione, androstenediol as well as other "over-the-counter" options like DHEA (dehydroepiandrosterone) and herbal remedies like Tribulus terrestris This review will focus on the use of these adjunct medications in isolation, or in combination with testosterone supplementation therapy as well as the biochemical nature of the supplements, the results of scientific trials as well as the side effects that limit their use. At the end of this review, physicians will have an improved understanding of the popular testosterone adjuncts being used currently as well as the availability of these substances and how they are used.
Topics: Androstenediol; Androstenedione; Dehydroepiandrosterone; Dietary Supplements; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Quality of Life; Testosterone; Time Factors
PubMed: 26272885
DOI: 10.1177/1557988315598554 -
The Journal of Steroid Biochemistry and... Nov 2021Associations of androstenediol, which has both androgenic and estrogenic activities, with circulating reproductive hormones and stress hormone in women during the...
Associations of androstenediol, which has both androgenic and estrogenic activities, with circulating reproductive hormones and stress hormone in women during the menopausal transition may be different depending on the menopausal stage. The aim of this study was to determine the changes in circulating androstenediol during the menopausal transition in Japanese women and the associations of androstenediol with estrogen, androgen and cortisol for each stage of the menopausal transition. We divided the 104 subjects into 6 stages by menstrual regularity and follicle-stimulating hormone level: mid reproductive stage, late reproductive stage, early menopausal transition, late menopausal transition, very early postmenopause and early postmenopause. Levels of dehydroepiandrosterone sulfate (DHEAS), estradiol, estrone, testosterone (T), free T, androstenedione and cortisol were measured. Serum androstenediol concentration was measured by using liquid chromatography mass spectrometry. There were no significant differences in androstenediol levels among the 6 stages. Levels of DHEA-S and testosterone showed significant and positive correlations with androstenediol in all stages. Estradiol levels showed negative correlations with androstenediol levels in the late menopausal transition and very early postmenopause (r=-0.452, p = 0.052 and r=-0.617, p = 0.006, respectively). Cortisol levels showed significant and positive correlations with androstenediol levels in the mid and late reproductive stages (r = 0.719, p = 0.003 and r = 0.808, p < 0.001, respectively).The associations of androstenediol with estradiol and cortisol were different depending on the stage of the menopausal transition. Androstenediol may play a compensatory role for estrogen deficiency from late menopausal transition to very early postmenopause.
Topics: Adult; Androgens; Androstenediol; Androstenedione; Cross-Sectional Studies; Dehydroepiandrosterone Sulfate; Estradiol; Estrogens; Female; Humans; Hydrocortisone; Japan; Menopause; Outpatients; Postmenopause; Testosterone
PubMed: 34571175
DOI: 10.1016/j.jsbmb.2021.106009 -
Biomedicine & Pharmacotherapy =... Jan 2020In the present study, the therapeutic effects of 5-androstenediol on radiation-induced myeloid suppression and tissue damage in mice and the possible mechanism were...
In the present study, the therapeutic effects of 5-androstenediol on radiation-induced myeloid suppression and tissue damage in mice and the possible mechanism were explored. The mice were subjected to whole-body irradiation, and 5-androstenediol was administered subcutaneously at different times and doses. The evaluation of the survival rate showed that the administration of 5-androstenediol every three days post-irradiation was the most effective in decreasing the death of the mice. Additionally, 5-androstenediol dose-dependently reduced the death caused by 9 Gy radiation. The pharmacological mechanism was investigated by blood analysis, western blot analysis, immunofluorescence and immunohistochemistry. 5-Androstenediol significantly ameliorated myeloid suppression, as demonstrated by elevated levels of total white blood cells, including neutrophils and platelets, in the peripheral blood. By H&E staining, we found that radiation-induced myeloid suppression in the bone marrow and spleen, as well as tissue damage in the lung and colon, was significantly ameliorated by treatment with 5-androstenediol. Immunohistochemistry showed elevated phosphorylation of p65 in the bone marrow and spleen, indicating the activation of NF-κB signaling. Moreover, 5-androstenediol markedly hampered the radiation-induced activation of caspase-1 and GSDMD in the colon by decreasing the interaction between AIM2 and ASC. Taken together, our results suggest that, by promoting NF-κB signaling and inhibiting inflammasome-mediated pyroptosis, 5-androstenediol can be used as a radioprotective drug.
Topics: Anabolic Agents; Androstenediol; Animals; DNA-Binding Proteins; Dose-Response Relationship, Drug; Female; Inflammasomes; Mice; Mice, Inbred C57BL; NF-kappa B; Radiation Injuries; Radiation-Protective Agents; Signal Transduction
PubMed: 31726369
DOI: 10.1016/j.biopha.2019.109597 -
Wound Repair and Regeneration :... 2009It is well recognized that stress of any nature will cause a delay in the wound healing response. This delayed healing response appears closely associated with immune...
It is well recognized that stress of any nature will cause a delay in the wound healing response. This delayed healing response appears closely associated with immune regulators. In this study, CD-1 mice were injected with a long acting form of methyl prednisolone to cause a steroid-induced immune suppression. After 24 hours, two 6-mm full thickness wounds were placed on the animals' backs and one group of animals received the immune-regulating hormone, androstenediol. Wound contraction was quantified by planimetry for the subsequent 14 days. Animals that were stressed with methyl prednisolone but receiving androstenediol contracted their open wounds at faster rates compared with methyl prednisolone-stressed animals treated with the vehicle alone. These findings suggest that restoration of immune regulation by androstenediol can reverse the delayed open wound contraction secondary to steroid stress.
Topics: Anabolic Agents; Androstenediol; Animals; Disease Models, Animal; Glucocorticoids; Male; Methylprednisolone; Mice; Skin; Wound Healing; Wounds and Injuries
PubMed: 19769728
DOI: 10.1111/j.1524-475X.2009.00528.x -
Medicinal Chemistry (Shariqah (United... Mar 2014Recently the benefit of subcutaneously applied dehydroepiandrosterone (DHEA) during sepsis was demonstrated. It was therefore supposed that the impact of DHEA might be...
BACKGROUND
Recently the benefit of subcutaneously applied dehydroepiandrosterone (DHEA) during sepsis was demonstrated. It was therefore supposed that the impact of DHEA might be induced by its metabolite androstenediol produced via conversion in subcutaneous tissue. Thus we postulate a comparable impact of intravenously applied androstenediol like DHEA.
MATERIAL AND METHODS
Male NMRI mice were subjected to sham-operation (laparotomy) or sepsis (cecal ligation and puncture). Animals received saline, DHEA (20 mg/kg/day) subcutaneously, androstenediol (20 mg/kg/day) subcutaneously and androstenediol (10 mg/kg/day) intravenously. During 48 h of sepsis and treatment clinical parameters such as survival and body temperature were observed. Termination of animals was performed 48 hrs after induction of sepsis in order to monitor splenocyte apoptosis (Annexin V binding capacity), cytokine release (IL-10 and TNF-α, ELISA), and immunological capacity by DTH-Reaction (Delayed type of hypersensitivity).
RESULTS
Subcutaneous and intravenous androstenediol administration improved the survival rate of septic mice 48 hrs after induction of CLP like subcutaneous administration of DHEA. (86% vs 53%). This effect was paralleled by a restoration of splenocyte proliferation and DTH reaction, a decreased cellular apoptosis rate of splenocytes, and an attenuation of cytokine release.
CONCLUSIONS
Administration of androstenediol induces an increased survival rate and improved cellular immune functions in septic mice. This effect was detected independent of the way of administration and is comparable to those effects induced by subcutaneous DHEA administration. With respect to clinical use during critical illness, intravenous administration of androstenediol seems to be an alternative to subcutaneous DHEA administration.
Topics: Administration, Intravenous; Androstenediol; Animals; Apoptosis; Body Temperature; Cytokines; Dehydroepiandrosterone; Disease Models, Animal; Dose-Response Relationship, Drug; Injections, Subcutaneous; Male; Mice; Mice, Inbred Strains; Molecular Conformation; Sepsis; Spleen; Survival Rate
PubMed: 23432316
DOI: 10.2174/157340641002140131155607 -
Menopause (New York, N.Y.) Dec 2015
Topics: Androstenediol; Androstenediols; Dehydroepiandrosterone; Endometrium; Female; Humans
PubMed: 26554883
DOI: 10.1097/GME.0000000000000558 -
Journal of Orthopaedic Trauma Aug 2011The pathogenesis of multiple organ dysfunction syndrome and sepsis after polytrauma is related to the posttraumatic immune response and the associated release of...
OBJECTIVES
The pathogenesis of multiple organ dysfunction syndrome and sepsis after polytrauma is related to the posttraumatic immune response and the associated release of inflammatory mediators. There exists a gender dimorphism in the posttraumatic host response. Sex steroids are believed to beneficially modulate the posttraumatic immune response. The specific effect of androstenediol on chemokines after trauma is unknown. We investigated whether the application of androstenediol has an effect on plasma chemokine levels and the associated remote organ damage in a two-hit mouse-model of trauma-hemorrhage, cecal ligation, and cecal puncture.
MATERIALS AND METHODS
Traumatic hemorrhage was induced followed by androstenediol application and volume resuscitation. Thereafter, androstenediol was given once daily in combination with a vehicle (Intralipid). The control group was injected with a solution containing only the vehicle at the same time points as the treatment groups' androstenediol applications. Sepsis was induced by cecal ligation and cecal puncture 48 hours afterward. Four hours after cecal ligation and cecal puncture, plasma measurements of chemokines were performed. Pulmonary infiltration by polymorphonuclear lymphocytes was measured by immunhistochemical staining and myeloperoxidase measurements were taken.
RESULTS
Application of androstenediol led to significantly decreased monocyte chemoattractant protein-1, monocyte chemoattractant protein-3, macrophage inflammatory protein-1α, and macrophage inflammatory protein-1β levels compared with the control animals after trauma-hemorrhage, cecal ligation, and cecal puncture (P < 0.05). Pulmonary infiltration and myeloperoxidase activity were significantly decreased in androstenediol-treated animals (P < 0.05).
CONCLUSION
Androstenediol modulates the immune response after trauma-hemorrhage, cecal ligation, and cecal puncture by reducing systemic chemokine levels, which are known to direct immune cells into the tissue possibly leading to organ damage. Androstenediol represents a potential therapeutic agent after major trauma in high-risk patients.
Topics: Anabolic Agents; Androstenediol; Animals; Chemokines; Hemorrhage; Immunity, Innate; Male; Mice; Mice, Inbred C57BL; Multiple Organ Failure; Sepsis; Wounds and Injuries
PubMed: 21738064
DOI: 10.1097/BOT.0b013e3182251044 -
The Journals of Gerontology. Series A,... Sep 2000Androstenediol (AED), a metabolite of dehydroepiandrosterone (DHEA) regulates innate and adaptive immune responses. To examine whether AED could effectively reverse the... (Comparative Study)
Comparative Study
Androstenediol (AED), a metabolite of dehydroepiandrosterone (DHEA) regulates innate and adaptive immune responses. To examine whether AED could effectively reverse the age-associated decline of antiviral immunity, 3-, 10-, and 22-month-old mice were treated with AED-sulfate (AED-S) for 45 days beginning 10 days prior to vaccination. Subsequently, mice were primed and boosted with suboptimal doses of a commercially-available trivalent influenza vaccine. Treatment of 10-month-old animals with AED-S during vaccination increased the titer of circulating antiviral immunoglobulin G to levels comparable with those in 3-month-old mice. Furthermore, AED-S treatment protected 10-month-old animals from intranasal challenge with a lethal dose of influenza virus 21 days after secondary vaccination. Although AED-S treatment of 22-month-old mice did not enhance vaccine responses and failed to protect against lethal challenge, the data from the 10-month-old animals suggest that treatment with AED-S will prevent the early manifestations of immunosenescence.
Topics: Age Factors; Aging; Anabolic Agents; Androstenediol; Animals; Chi-Square Distribution; Germ-Free Life; Immunity, Active; Immunization, Secondary; Immunocompetence; Immunoglobulin G; Influenza A virus; Influenza Vaccines; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Time Factors; Treatment Outcome; Vaccination
PubMed: 10995038
DOI: 10.1093/gerona/55.9.b418