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Title: 17β-trenbolone, an anabolic–androgenic steroid as well as an environmental hormone, contributes to neurodegeneration

Both genetic and environmental factors contribute to neurodegenerative disorders. In a large number of neurodegenerative diseases (for example, Alzheimer's disease (AD)), patients do not carry the mutant genes. Other risk factors, for example the environmental factors, should be evaluated. 17β-trenbolone is a kind of environmental hormone as well as an anabolic–androgenic steroid. 17β-trenbolone is used as a growth promoter for livestock in the USA. Also, a large portion of recreational exercisers inject 17β-trenbolone in large doses and for very long time to increase muscle and strength. 17β-trenbolone is stable in the environment after being excreted. In the present study, 17β-trenbolone was administered to adult and pregnant rats and the primary hippocampal neurons. 17β-trenbolone's distribution and its effects on serum hormone levels and Aβ42 accumulation in vivo and its effects on AD related parameters in vitro were assessed. 17β-trenbolone accumulated in adult rat brain, especially in the hippocampus, and in the fetus brain. It altered Aβ42 accumulation. 17β-trenbolone induced apoptosis of primary hippocampal neurons in vitro and resisted neuroprotective function of testosterone. Presenilin-1 protein expression was down-regulated while β-amyloid peptide 42 (Aβ42) production and caspase-3 activities were increased. Both androgen and estrogen receptors mediated the processes. 17β-trenbolone played critical roles inmore » neurodegeneration. Exercisers who inject large doses of trenbolone and common people who are exposed to 17β-trenbolone by various ways are all influenced chronically and continually. Identification of such environmental risk factors will help us take early prevention measure to slow down the onset of neurodegenerative disorders. - Highlights: • The widely used anabolic–androgenic steroid 17β-trenbolone has neurotoxicity. • 17β-trenbolone crosses the blood brain barrier and placental barrier. • Rat has high level of 17β-trenbolone in hippocampus after intramuscular injection. • 17β-trenbolone induces apoptosis of primary hippocampal neurons. • 17β-trenbolone affects Alzheimer's disease-related proteins Aβ42 and presenilin-1.« less
Authors:
 [1] ;  [2] ;  [3]
  1. Wenzhou Institute of Biomaterials and Engineering, No. 16 Xinshan Road, Hi-tech Industry Park, Wenzhou (China)
  2. (China)
  3. Key Laboratory of Animal Resistance, College of Life Science, Shandong Normal University, 88 East Wenhua Road, Jinan 250014 (China)
Publication Date:
OSTI Identifier:
22439943
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 282; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADULTS; APOPTOSIS; BLOOD-BRAIN BARRIER; CEREBROSPINAL FLUID; DIFFUSION BARRIERS; ENVIRONMENT; FETUSES; GENES; HIPPOCAMPUS; INTRAMUSCULAR INJECTION; MEMBRANES; MITOCHONDRIA; MUTANTS; NERVE CELLS; NERVOUS SYSTEM DISEASES; RATS; RECEPTORS; TESTOSTERONE; USA