Androstenediol regulates systemic resistance against lethal infections in mice

Abstract

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.

Serum Concentration of Androstenediol and Androstenediol Sulfate in Patients with Hyperthyroidism and Hypothyroidism.

“…Moreover, ADIOL TAGAWA et al has been reported to be a more biologically active metabolite than dehydroepiandrosterone (DHEA). For example, ADIOL was at least 100-fold more effective in up-regulating systemic resistance against Coxsackie virus infection [7,8].…”

Beta-Androstenes and Resistance to Viral and Bacterial Infections

“…Based on animal examination, it appeared that DHEA was converted in vivo, and we assumed that ␤ AED was the active agent. Consequently, a comparison of the effects of ␤ AED and DHEA on lethal CB4 infections in C57BL/6J mice was performed [16] . The results in table 1 demonstrate that CB4 infection at a dose of 10 4 PFU per animal was lethal in 100% of the animals.…”

Beta Androstenediol Mitigates the Damage of 1 GeV/n Fe Ion Particle Radiation to the Hematopoietic System

“…The effects of AED are mediated by an increase in host resistance and not by a direct antibacterial or antiviral effect, and a restoration of myelopoeisis after irradiation. [6][7][8][9]26,27 The data presented in this initial report indicate that in addition to restoration from gamma radiation injury, AED also mitigates the damages from high LET charged particle radiation exposure. Since bacteria such as Pseudomonas aeruginosa and Cepacia burkholderi, as well as opportunistic species such as Streptococcus pneumoniae, have been shown to be infectious to individuals with weakened immune systems, they may be potential pathogens for crew members in space.…”

“…Previous reports demonstrated that a single subcutaneous injection of AED protects the host from death and restores radiation-mediated destruction of the myelopoeitic system after exposure to wholebody gamma radiation dose of 8 Gy (LD100 for C57BL/6J; human LD100 6 Gy). [6][7][8][9] Gridley et al 10,11 and Pecaut et al 12,13 have reported on the acute effects of whole-body iron particle radiation to C57BL/6J mice. Four days after exposure to a dose of 3 Gy, spleen weight was reduced by 52% and white blood cell (WBC) counts, monocytes, and lymphocytes levels were reduced by about 80%.…”

“…Previously, Loria et al [6][7][8]26,27 reported that AED protected C57BL/6J mice from death after lethal infection challenge by Pseudomonas, Klebsiella pneumonia, Enterococcus faecalis, Coxsackievirus, Influenza, and different viruses causing encephalitis. Further, a single subcutaneous injection of AED restored the hosts' myelopoeitic system to normal by 21 days after whole-body radiation exposure to a lethal dose of 8-Gy gamma radiation.…”