PMID- 16638015
OWN - NLM
STAT- MEDLINE
DCOM- 20060818
LR  - 20101118
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 98
IP  - 2
DP  - 2006 Jul
TI  - A neuroactive steroid 5alpha-androstane-3alpha,17beta-diol regulates androgen 
      receptor level in astrocytes.
PG  - 355-63
AB  - Optic nerve head (ONH) astrocytes from patients with glaucomatous optic 
      neuropathy exhibit increased production of 5alpha-androstane-3alpha,17beta-diol 
      (3alpha-diol), a neuroactive metabolite of 5alpha-dihydrotestosterone 
      (5alpha-DHT). To determine whether ONH astrocytes are androgen target cells, and 
      whether 3alpha-diol is capable of regulating astrocyte functions, we studied the 
      response of human ONH astrocytes to 3alpha-diol compared with 
      17beta-hydroxy-17alpha-methyl-estra-4,9,11-trien-3-one (R1881), a synthetic 
      5alpha-DHT agonist. In ONH astrocytes, both 3alpha-diol and R1881 increased 
      protein levels of androgen receptor (AR) and glial fibrillary acidic protein 
      (GFAP), however, only R1881 also increased the AR mRNA level and astrocyte 
      proliferation. Both R1881 and 3alpha-diol rapidly activate the mitogen-activated 
      protein kinase (MAPK) signaling pathway in ONH astrocytes, as confirmed by 
      phosphorylation of extracellular signal-regulated kinase (ERK). 3Alpha-diol also 
      activates the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) 
      pathway. 3Alpha-diol regulates the increase of AR protein level and the 
      phosphorylation through the PI3K/Akt pathway, whereas R1881 regulates them 
      through the MAPK/ERK pathway. Our findings demonstrate that human ONH astrocytes 
      are androgen target cells and respond to androgens by the rapid activation of 
      cell signaling. The activation of the PI3K/Akt pathway by 3alpha-diol may 
      regulate various properties of astrocytes, including cell motility and survival, 
      and may play a role in the formation and maintenance of the reactive phenotype of 
      ONH astrocytes in glaucoma.
FAU - Agapova, Olga A
AU  - Agapova OA
AD  - Department of Ophthalmology and Visual Sciences, Washington University, School of 
      Medicine, Saint Louis, Missouri 63110, USA. Agapova@vision.wustl.edu
FAU - Malone, Paula E
AU  - Malone PE
FAU - Hernandez, M Rosario
AU  - Hernandez MR
LA  - eng
GR  - EY-02687/EY/NEI NIH HHS/United States
GR  - EY-06416/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060421
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Androgens)
RN  - 0 (Receptors, Androgen)
RN  - 25126-76-5 (Androstane-3,17-diol)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Androgens/pharmacology
MH  - Androstane-3,17-diol/*pharmacology
MH  - Astrocytes/drug effects/*metabolism
MH  - Blotting, Western
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Immunoprecipitation
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Oncogene Protein v-akt/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Receptors, Androgen/drug effects/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/physiology
EDAT- 2006/04/28 09:00
MHDA- 2006/08/19 09:00
CRDT- 2006/04/28 09:00
PHST- 2006/04/28 09:00 [pubmed]
PHST- 2006/08/19 09:00 [medline]
PHST- 2006/04/28 09:00 [entrez]
AID - JNC3879 [pii]
AID - 10.1111/j.1471-4159.2006.03879.x [doi]
PST - ppublish
SO  - J Neurochem. 2006 Jul;98(2):355-63. doi: 10.1111/j.1471-4159.2006.03879.x. Epub 
      2006 Apr 21.