PMID- 27754784
OWN - NLM
STAT- MEDLINE
DCOM- 20170526
LR  - 20170526
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Linking)
VI  - 157
IP  - 12
DP  - 2016 Dec
TI  - 5alpha-Androstane-3alpha,17beta-Diol Inhibits Neurotoxicity in SH-SY5Y Human Neuroblastoma 
      Cells and Mouse Primary Cortical Neurons.
PG  - 4570-4578
AB  - Low free T levels in men are associated with age-related cognitive decline and 
      increased risk for neurotoxicity, resulting in disease. The mechanisms underlying 
      these observations remain poorly defined. Although rapid, androgen 
      receptor-dependent activation of ERK has been postulated as a neurotrophic and 
      neuroprotective mechanism, actions of T metabolites such as 
      5alpha-androstane-3alpha,17beta-diol (3alpha-diol) may also be involved. We investigated the 
      influence of 3alpha-diol on the induction of ERK phosphorylation in SH-SY5Y human 
      female neuroblastoma cells and primary cortical neurons from male and female 
      mice. In SH-SY5Y cells, ERK phosphorylation was induced by 10 nM DHT, epidermal 
      growth factor, hydrogen peroxide (H(2)O(2)), and acetylcholine. The addition of 
      10 nM 3alpha-diol, which did not itself activate ERK, significantly inhibited ERK 
      phosphorylation induced by DHT, epidermal growth factor, or H(2)O(2), but not 
      acetylcholine. In both SH-SY5Y cells and primary cortical neurons, prolonged ERK 
      phosphorylation and caspase-3 cleavage resulting from amyloid beta-peptide 1-42 
      (Abeta42) exposure were inhibited by cotreatment with 3alpha-diol. 3alpha-diol also reduced 
      the loss in cellular viability induced by Abeta42 or H(2)O(2) in SH-SY5Y cells. 
      These data suggest that T-mediated neuroprotection may occur via two distinct but 
      complementary mechanisms: an initial rapid activation of ERK phosphorylation, 
      followed by modulation via 3alpha-diol of the potentially adverse consequences of 
      prolonged ERK activation.
FAU - Mendell, A L
AU  - Mendell AL
AD  - Department of Biomedical Sciences (A.L.M., C.E.C., B.E.K., N.J.M.), Ontario 
      Veterinary College, University of Guelph, Guelph, Ontario, Canada, N1G 2W1.
FAU - Creighton, C E
AU  - Creighton CE
AD  - Department of Biomedical Sciences (A.L.M., C.E.C., B.E.K., N.J.M.), Ontario 
      Veterinary College, University of Guelph, Guelph, Ontario, Canada, N1G 2W1.
FAU - Kalisch, B E
AU  - Kalisch BE
AD  - Department of Biomedical Sciences (A.L.M., C.E.C., B.E.K., N.J.M.), Ontario 
      Veterinary College, University of Guelph, Guelph, Ontario, Canada, N1G 2W1.
FAU - MacLusky, Neil J
AU  - MacLusky NJ
AD  - Department of Biomedical Sciences (A.L.M., C.E.C., B.E.K., N.J.M.), Ontario 
      Veterinary College, University of Guelph, Guelph, Ontario, Canada, N1G 2W1.
LA  - eng
PT  - Journal Article
DEP - 20161018
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Amyloid beta-Peptides)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 25126-76-5 (Androstane-3,17-diol)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 3.4.22.- (Caspase 3)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/pharmacology
MH  - Amyloid beta-Peptides/pharmacology
MH  - Androstane-3,17-diol/*pharmacology
MH  - Animals
MH  - Caspase 3/metabolism
MH  - Cell Line, Tumor
MH  - Cerebral Cortex/*drug effects/metabolism
MH  - Dihydrotestosterone/pharmacology
MH  - Epidermal Growth Factor/pharmacology
MH  - Female
MH  - Humans
MH  - Hydrogen Peroxide/pharmacology
MH  - MAP Kinase Signaling System/*drug effects
MH  - Male
MH  - Mice
MH  - Neuroblastoma/metabolism
MH  - Neurons/*drug effects/metabolism
MH  - Phosphorylation/drug effects
EDAT- 2016/10/19 06:00
MHDA- 2017/05/27 06:00
CRDT- 2016/10/19 06:00
PHST- 2016/10/19 06:00 [pubmed]
PHST- 2017/05/27 06:00 [medline]
PHST- 2016/10/19 06:00 [entrez]
AID - 10.1210/en.2016-1508 [doi]
PST - ppublish
SO  - Endocrinology. 2016 Dec;157(12):4570-4578. doi: 10.1210/en.2016-1508. Epub 2016 
      Oct 18.