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Steroids Nov 2014Women with polycystic ovary syndrome (PCOS) show high prevalence of endometrial hyperplasia and adenocarcinoma. Endometrial proliferation is increased, evaluated by high...
Women with polycystic ovary syndrome (PCOS) show high prevalence of endometrial hyperplasia and adenocarcinoma. Endometrial proliferation is increased, evaluated by high levels of Ki67 (cell cycle marker) and low levels of p27 (negative regulator of cell cycle). Nevertheless, endometrial changes in cyclin D1 (positive regulator of cell cycle) in PCOS-women are not described. Androst-5-ene-3β,17β-diol (androstenediol), steroid with estrogenic activity present in endometria, could be related to increased endometrial cell proliferation. The objective of this study was to determine protein content of cyclin D1 and androstenediol levels in endometria from PCOS and control-women and to evaluate the possible mechanism favoring cell proliferation associated with hormonal characteristics of patients. Therefore, cyclin D1 protein content in PCOS-women and control-endometrial tissue were assessed by western blot and immunohistochemistry. The androstenediol levels were evaluated by ELISA. To further analyze the effect of steroids (androstenediol, 17β-estradiol, testosterone) in cell proliferation, levels of proteins cyclin D1, p27 and Ki67 were evaluated in an in vitro model of stromal endometrial cells T-HESC and St-T1b. An increase in cyclin D1 and androstenediol was observed in tissues from PCOS-women relative to control group (p<0.05). In the in vitro model, androstenediol exerted increase in cyclin D1 (p<0.05) and a decrease in p27 protein level (p<0.05), while Ki67 in St-T1b cells increased under this stimulus (p<0.05). Testosterone produces opposite effects in the levels of the above markers (p<0.05). Therefore, the hormonal imbalance associated with this syndrome could alter endometrial tissue homeostasis, promoting cell proliferation. Androstenediol is a molecule that could be involved by stimulating proliferation, whereas testosterone elicits a role of cell cycle repressor.
Topics: Adult; Androstenediol; Androstenedione; Cell Proliferation; Cyclin D1; Endometrium; Female; Humans; Polycystic Ovary Syndrome; Progesterone; Proliferating Cell Nuclear Antigen; Testosterone
PubMed: 25065586
DOI: 10.1016/j.steroids.2014.07.008 -
Obstetrics and Gynecology Clinics of... Sep 2011The concept that adrenal androgen production gradually declines with age has changed after analysis of longitudinal data from the Study of Women's Health Across the... (Review)
Review
The concept that adrenal androgen production gradually declines with age has changed after analysis of longitudinal data from the Study of Women's Health Across the Nation (SWAN). It is now recognized that 4 adrenal androgens rise during the menopausal transition in most women. Ethnic and individual differences in sex steroids are more apparent in circulating adrenal steroids than in either estradiol or cyclic ovarian steroid hormone profiles, particularly during the early and late perimenopause. Thus, adrenal steroid production may play a larger role in the occurrence of symptoms and the potential for healthier aging than previously recognized.
Topics: Adrenal Cortex Hormones; Adrenal Glands; Androgens; Androstenediol; Dehydroepiandrosterone Sulfate; Female; Humans; Perimenopause; Testosterone
PubMed: 21961714
DOI: 10.1016/j.ogc.2011.06.001 -
Molecular Pharmacology Aug 20075-Androstenediol (5-AED) stimulates hematopoiesis and enhances survival in animals exposed to ionizing radiation (IR), suggesting that this steroid may act on...
5-Androstenediol promotes survival of gamma-irradiated human hematopoietic progenitors through induction of nuclear factor-kappaB activation and granulocyte colony-stimulating factor expression.
5-Androstenediol (5-AED) stimulates hematopoiesis and enhances survival in animals exposed to ionizing radiation (IR), suggesting that this steroid may act on hematopoietic progenitor cells. We used gamma-irradiated primary human CD34(+) hematopoietic progenitor cells to show that 5-AED protects hematopoietic cells from IR damage, as shown by enhanced cell survival, clonogenicity, proliferation, and differentiation. Unlike in tumor cells, IR did not induce nuclear factor-kappaB (NFkappaB) activation in primary progenitors. However, IR stimulated IkappaB(beta) release from NFkappaB/IkappaB complexes and caused NFkappaB1 (p50) degradation. 5-AED stabilized NFkappaB1 in irradiated cells and induced NFkappaB gene expression and NFkappaB activation (DNA binding). 5-AED stimulated interleukin-6 and granulocyte colony-stimulating factor (G-CSF) secretion. The survival-enhancing effects of 5-AED on clonogenic cells were abrogated by small interfering RNA inhibition of NFkappaB gene expression and by neutralization of G-CSF with antibody. The effects of 5-AED on survival and G-CSF secretion were blocked by the NFkappaB inhibitor N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal (MG132). 5-AED had no effect on accumulation of the proapoptotic factor p53 after IR, as determined by Western blot. The results indicate that NFkappaB1 degradation after IR may be responsible for the radiation sensitivity of CD34+ cells compared with tumor cells. 5-AED exerts survival-enhancing effects on irradiated human hematopoietic progenitor cells via induction, stabilization, and activation of NFkappaB, which results in increased secretion of hematopoietic growth factor G-CSF.
Topics: Androstenediol; Antigens, CD34; Cell Differentiation; Cell Survival; Cells, Cultured; DNA-Activated Protein Kinase; Gamma Rays; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cells; Humans; I-kappa B Proteins; Interleukin-6; NF-kappa B; Tumor Suppressor Protein p53
PubMed: 17473057
DOI: 10.1124/mol.107.035394 -
International Immunopharmacology Apr 2007We previously reported that five daily intramuscular doses of 5-androstenediol (AED), a naturally occurring adrenal steroid hormone, stimulated multilineage recovery of...
We previously reported that five daily intramuscular doses of 5-androstenediol (AED), a naturally occurring adrenal steroid hormone, stimulated multilineage recovery of bone marrow in rhesus monkeys with radiation-induced myelosuppression after 4.0 Gy total body irradiation (TBI). Here we report the effect of AED on the survival of eighty rhesus macaques that received a 6.0 Gy dose of TBI in four sequential pilot studies. The drug was administered intramuscularly, based on body weight, 2-4 h after irradiation and continued once daily for a total of five injections. No clinical support in the form of antibiotics or transfusions was given to the animals at any time during the study. Five of the 40 (12.5%) treated animals died, compared to 13 of 40 (32.5%) of the animals in the control group (p=0.032). The combination of accumulated days of thrombocytopenia (<20,000 platelets/microL) up to day 14 (before the first death) together with treatment, accurately predicts mortality (p<0.001). The compound significantly reduced the duration of thrombocytopenia and neutropenia (p<0.01). The accumulation of days of neutropenia (ANC<500 cells/microL) up to day 14 plays no major role in predicting death. AED shows significant activity in irradiated primates with acute hematopoietic radiation syndrome.
Topics: Androstenediol; Animals; Female; Gamma Rays; Macaca mulatta; Male; Radiation Injuries, Experimental; Radiation-Protective Agents; Thrombocytopenia; X-Rays
PubMed: 17321473
DOI: 10.1016/j.intimp.2006.12.005 -
International Immunopharmacology Nov 2006Total body ionizing irradiation (TBI) between 2-8 Gy causes the hematopoietic component of the acute radiation syndrome (ARS) in humans. Here we report on an exploratory...
Total body ionizing irradiation (TBI) between 2-8 Gy causes the hematopoietic component of the acute radiation syndrome (ARS) in humans. Here we report on an exploratory study with 5-androstenediol (AED) in rhesus monkeys exposed to 4 Gy (60)Co gamma TBI. In this study, the effects of two formulations administered 3-4 h after irradiation were evaluated. After radiation, severe neutropenia (<500 neutrophils/microL), thrombocytopenia (<50,000 platelets/microL), and anemia (hemoglobin <8.0 g/dL) occurred in 6, 6, and 5 of the 6 control animals, respectively. In these 6 control animals, the median time to first day of each defined cytopenia was 8.5, 13, and 20 days and the median time to last occurrence was 22.5, 19.5 and 29.5 days, respectively. All treated groups had a decrease in the duration of severe neutropenia relative to vehicle control. All but one dosing regimen decreased the duration of thrombocytopenia and anemia. Five consecutive days of a 15 mg/kg intramuscular (IM) micro-particle preparation and a once weekly 15 mg/kg subcutaneous (SC) nanoparticle suspension generally provided the greatest radiation protection. AED, as a single agent, promotes multilineage hematopoietic recovery of the bone marrow. These data suggest that it may play an important therapeutic role in the management of acute radiation syndrome.
Topics: Androstenediol; Anemia; Animals; Female; Hematopoiesis; Macaca mulatta; Male; Neutropenia; Particle Size; Radiation Injuries, Experimental; Thrombocytopenia; Whole-Body Irradiation
PubMed: 16979125
DOI: 10.1016/j.intimp.2006.07.005 -
Experimental Biology and Medicine... Jul 2001
Topics: Androstenediol; Animals; Female; Gamma Rays; Killer Cells, Natural; Leukocyte Count; Male; Mice; Monocytes; Neutropenia; Radiation Injuries; Radiation-Protective Agents; Thrombocytopenia; Whole-Body Irradiation
PubMed: 11444097
DOI: 10.1177/153537020222600707 -
American Journal of Obstetrics and... Sep 1951
Topics: Androstenediol; Female; Genital Diseases, Female; Humans
PubMed: 14877935
DOI: 10.1016/0002-9378(51)91170-2 -
Immunopharmacology and Immunotoxicology 2005We compared in vivo radioprotective efficacy of 5-androstenediol (5-AED) to that of ten other steroids: 17alpha-androstenediol, dehydroepiandrosterone, 5-androstenetriol... (Comparative Study)
Comparative Study
We compared in vivo radioprotective efficacy of 5-androstenediol (5-AED) to that of ten other steroids: 17alpha-androstenediol, dehydroepiandrosterone, 5-androstenetriol (AET), 4-androstenedione (AND), testosterone, estradiol, fluasterone, 16alpha-bromoepiandrosterone, 16alpha-fluoro-androst-5-en-17alpha-ol (alpha-fluorohydrin, AFH), and 16alpha-fluoro-androst-5-en-17beta-ol (beta-fluorohydrin). Steroids were administered 24 or 48 hr before, or 1 hr after, whole-body gamma-irradiation. Two days after irradiation at 3 Gy, blood elements were counted. In addition, after irradiation at 9-12.5 Gy, survival was recorded for 30 days. The results showed radioprotective efficacy was specific for 5-AED. One other steroid, AFH, demonstrated appreciable survival effects but was less efficacious than 5-AED. AND and AET produced slight enhancement of survival in some experiments. This is the first demonstration that the prophylactic window for survival enhancement by 1 subcutaneous (s.c.) injection of 5-AED is as long as 48 hr in mice. Moreover, the results indicate that 1 s.c. injection of 5-AED 1 hr after irradiation is much less effective than 1 injection 24-48 hr before irradiation. Comparing the molecular features of steroids with radioprotective efficacy leads to the following conclusions: 1) these effects are due to interaction with specific receptors, since s.c. injection of extremely similar molecules with the same physicochemical properties as 5-AED were not radioprotective; 2) the 17-hydroxyl group is essential; 3) this group must be in the beta configuration in the absence of nearby side groups; 4) a halogen atom at 16 changes the 17-hydroxyl specificity to alpha; 5) the 3beta-hydroxyl group is not essential; 6) addition of a 7beta-hydroxyl group is deleterious; and 7) the effects are not due to activation of sex steroid receptors.
Topics: Androstenediol; Animals; Female; Gamma Rays; Leukocyte Count; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred DBA; Neutrophils; Radiation-Protective Agents
PubMed: 15803857
DOI: 10.1081/iph-51289 -
PloS One 2021Animal experiments have consistently shown that estrogen receptor β (ERβ)-selective ligands have antidepressant and anxiolytic effects. In humans, endogenous ligands...
Animal experiments have consistently shown that estrogen receptor β (ERβ)-selective ligands have antidepressant and anxiolytic effects. In humans, endogenous ligands for ERβ include 5α-androstane-3β, 17β-diol (3βAdiol) and androstenediol (Δ5-diol). We determined, for the first time, the exact serum levels of 3βAdiol and Δ5-diol in young healthy volunteers using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We investigated the effect of the menstrual cycle on the levels of these steroids in women; then, we performed a gender comparison. Blood samples were collected from 48 subjects: 23 women (mean age = 28.4±7.8 years) and 25 men (mean age = 31.4±7.8 years). We collected the blood samples of women at three time-points in the menstrual cycle: the early follicular phase, ovulatory or mid-cycle phase, and mid-luteal phase. A total of 92 blood samples were analyzed using LC-MS/MS. The levels of two well-studied steroids, namely dehydroepiandrosterone (DHEA) and 17β-estradiol (E2), were simultaneously measured. Depression rating scale (Hamilton Rating Scale for Depression, Beck Depression Inventory-II and Quick Inventory of Depressive Symptomatology) scores were also recorded at the time of blood sampling. Significant differences in the levels of 3βAdiol and E2 and in the depression rating scale scores were observed over the duration of the menstrual cycle of the women. The levels of 3βAdiol and Δ5-diol were significantly lower in women than in men. E2 levels were higher in women than in men, and DHEA levels did not differ significantly between men and women. Further, women had higher scores than men on the Hamilton Rating Scale for Depression. Sex differences in depressive symptoms can be explained by 3βAdiol and Δ5-diol levels, and the effect of the menstrual cycle on mood can be explained by 3βAdiol and E2 levels, not by Δ5-diol level.
Topics: Adult; Androstenediol; Chromatography, Liquid; Dehydroepiandrosterone; Estradiol; Female; Humans; Male; Menstrual Cycle; Sex Characteristics; Tandem Mass Spectrometry; Young Adult
PubMed: 34910781
DOI: 10.1371/journal.pone.0261440 -
Annals of the New York Academy of... Jun 1993
Topics: Androstenediols; Animals; Coxsackievirus Infections; Dehydroepiandrosterone; Enterovirus B, Human; Immunity, Innate; Immunologic Factors; Mice; Mice, Inbred C57BL
PubMed: 8395779
DOI: 10.1111/j.1749-6632.1993.tb35878.x