Androstenediol stimulates myelopoiesis and enhances resistance to infection in gamma-irradiated mice

Whitnall, Mark H.; Elliott, Thomas B.; Harding, Rita A.; Inal, Cynthia E.; Landauer, Michael R.; Wilhelmsen, Catherine L.; McKinney, LuAnn; Miner, Venita; Jackson, William E.; Loria, Roger M.; Ledney, G D; Seed, Thomas M.

doi:10.1016/s0192-0561(99)00059-4

Cited by 109 publications

(78 citation statements)

References 51 publications

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“…ADIOL has been suggested to have immunoregulatory activity and enhances resistance to infection in animal experiment [46,47]. Furthermore, ADIOL may down-regulate the Th2 immune re-TAGAWA et al…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2001

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Abstract.Androstenediol (5-androsten-3 j3, 17~-diol, ADIOL) and androstenediol 3-sulfate (ADIOLS) are active metabolites of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS), respectively, and have estrogenic activity and immunoregulatory function.We examined serum concentrations of ADIOL, ADIOLS, DHEA, DHEAS and pregnenolone sulfate (5-pregnen-3j3-o1-20-one sulfate, PREGS) in patients with Graves' thyrotoxicosis (male/female 9/14), hypothyroidism (11/20) and in normal controls (14/29). In hypothyroidism serum levels of all these steroids were significantly decreased in both genders. In hyperthyroidism, in contrast, serum levels of ADIOLS (male 1.49±0.69, female 0.64±0.31 imol/I), DHEAS (male 7.43±3.91, female 5.13±2.03 tcmol/1), and PREGS (male 1.13±0.58, female 1.07±0.85 timol/I) were markedly increased, but serum concentrations of ADIOL and DEHA were not significantly different from controls (ADIOLS male 0.36±0.33, female 0.14±0.09 pmol/1; DHEAS male 2.88± 1.70, female 1.86± 1.03 pmol/1; PREGS male 0.18±0.12, female 0.11 ±0.08 pmol/l; ADIOL male 3.76±1.35, female 1.91 ± 1.17 nmol/l; DHEA male 9.23±3.49, female 13.5± 10.8 nmol/1). Serum concentrations of all these steroids correlated with the serum concentration of the thyroid hormones in these patients.Serum albumin and sex hormone-binding globulin concentrations were not related to these changes in the concentrations of steroids. These findings indicate that serum concentrations of ADIOLS, ADIOL, DHEAS, DHEA and PREGS were decreased in hypothyroidism, whereas serum ADIOLS, DHEAS and PREGS concentrations were increased but ADIOL and DHEA were normal in hyperthyroidism.Thyroid hormone may stimulate the synthesis of these steroids and sulfotransferase is speculated to be increased in hyperthyroidism. Increased ADIOLS might contribute to menstrual disturbances and gynecomastia in hyperthyroidism.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2001

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“…At that time, TPO was not approved as a pharmaceutical drug as it was necessary to increase the number of platelets. 44,45) On March 11, 2006, a 50-year-old Caucasian male worker in a 60 Co -radiation sterilization facility (speci c activity, 800.000 Ci; dose rate 5 kGy/h) was exposed to the cobalt-60 sources (total activity 3 × 10 4 TBq) for 20 seconds, with an estimated total body irradiation of 4,2 Gy (3,8-5 Gy). On day 20 (March 31, 2006), the patient was admitted to the Percy Hospital (Clamart, France).…”

Section: )mentioning

confidence: 99%

“…9) WHITNALL et al have investigated that a single subcutaneous injection of 5-AED 24 to 48 h prior to or 2 h after a lethal dose of TBI enhanced survival in mice, 60,61) although an injection 2 h after irradiation had lower ef cacy than a pre-irradiation injection (i.e., 12% vs. 78%, respectively). 62) They have investigated radioprotective ef cacy of eleven steroids, 5-AED, 17 -androstenediol, dehydroepiandrosterone, 5-androstenetriol, 4-androstenedione, testosterone, estradiol, uasterone, 16 -bromoepiandrosterone, 16 -uoro-androst-5-en-17 -ol ( -uorohydrin), and 16 -uoro-androst-5-en-17 -ol ( -uorohydrin) against mice 9-12.5 Gy for survival studies.…”

Section: Cblb502mentioning

confidence: 99%

“…65) Moreover, GT3 increased expression of the DNA-repair gene RAD50 and attenuated radiation-induced RAD50 suppression. Currently, GT3 is being investigated for its ef cacy against 60 Co -irradiation using a NHP model. 9) On the other hand, LI et al have investigated DT3 on CD2F1 mice and human hematopoietic progenitor CD34 + cells exposed -irradiation, showing the signi cant radioprotective effects.…”

Section: Cblb502mentioning

confidence: 99%

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Overview of Radiation-protective Agent Research and Prospects for the Future

Kashiwakura

2017

Jpn. J. Health Phys.

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Since the discovery of X-rays in 1895, radioactivity and its effects on the body have led to the issue of radiation injury. Radiation-related casualties following exposure to a lethal dose of ionizing radiation show severe acute radiation syndromes (ARS) involving bone marrow death and gastrointestinal death. ARS causes a decrease in the peripheral blood cell count and such as severe ARS, the intake of appropriate medications is the most suitable initial treatment. Therefore, the development of effective radiation-protective agent is an important issue against radiological accidents and nuclear threats. In this review, the overview of radiation-protective/mitigative agent development against acute radiation effects (external exposure), as well as our research data, and the prospects for future research have been outlined.

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“…With this in mind, considerable progress has been made in the development of radioprotectants 8,9 . There are several radiation countermeasures at different stages of development [10][11][12][13][14] 9,[15][16][17] . The human hematopoietic system is highly susceptible to radiation injury.…”

Section: Introductionmentioning

confidence: 99%

Progenitor Cells as a Bridging Therapy for Radiation Casualties

Singh

Brown

Singh

et al. 2011

DSJ

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Hematopoiesis is the process by which daughter cells of multipotential, self-renewing stem cells progress along differentiation pathways to become progressively more committed to specific lineages while losing their self-renewal capacity. Leucopenia and thrombocytopenia after ionising radiation exposure are due largely to injury to stem cells and progenitors in the hematopoietic tissue of the bone marrow; and in mice, the spleen. Recovery depends on the ability of the remaining stem cells and progenitors to proliferate and differentiate sufficiently to reconstitute the immune system before it is challenged by potential microorganisms and lethal infections occur. This mini review discusses various approaches to the mobilisation of progenitors and their utility as a bridging therapy for radiation casualties.

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Androstenediol stimulates myelopoiesis and enhances resistance to infection in gamma-irradiated mice

Cited by 109 publications

References 51 publications

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

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

Overview of Radiation-protective Agent Research and Prospects for the Future

Progenitor Cells as a Bridging Therapy for Radiation Casualties

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