PMID- 24423637
OWN - NLM
STAT- MEDLINE
DCOM- 20140313
LR  - 20140115
IS  - 1554-6578 (Electronic)
IS  - 0022-3069 (Linking)
VI  - 73
IP  - 2
DP  - 2014 Feb
TI  - Gender differences in multiple sclerosis: induction of estrogen signaling in male 
      and progesterone signaling in female lesions.
PG  - 123-35
LID - 10.1097/NEN.0000000000000037 [doi]
AB  - The basis of gender differences in the prevalence and clinical progression of 
      multiple sclerosis (MS) is not understood. Here, we identify gender-specific 
      responses in steroid synthesis and signaling in the brains of MS patients as 
      possible contributors to these differences. We investigated gene expression 
      changes in these pathways and of inflammatory cytokines in MS lesions and 
      normal-appearing white matter (NAWM) of male and female patients (n=21) and 
      control NAWM (n=14) using quantitative polymerase chain reaction (25 MS lesions, 
      21 MS NAWM, and 14 control NAWM) and immunohistochemistry (3-4 sections per 
      group). In MS lesions in males, there was local upregulation of aromatase (an 
      enzyme involved in estrogen biosynthesis), estrogen receptor-beta (ERbeta), and tumor 
      necrosis factor (TNF) mRNA; whereas in females, there was local upregulation of 
      3beta-hydroxysteroid-dehydrogenase, a progesterone synthetic enzyme, and of 
      progesterone receptor. Astrocytes in the rim and center of MS lesions were found 
      to be the primary source of steroidogenic enzyme and receptor expression. 
      Aromatase and ERalpha mRNA levels were positively correlated with that of TNF in 
      primary cultures of human microglia and astrocytes; TNF caused increased ERalpha, 
      suggesting that inflammatory signals stimulate estrogen signaling in this cell 
      type. Together, these findings suggest that there are gender differences in the 
      CNS of MS patients that may affect lesion pathogenesis, that is, in males, 
      estrogen synthesis and signaling are induced; whereas in females, progestogen 
      synthesis and signaling are induced. These differences may represent contributing 
      factors to gender differences in the prevalence and course of MS.
FAU - Luchetti, Sabina
AU  - Luchetti S
AD  - From the Departments of Neuroimmunology (SL, CGvE, KS, IH), Astrocyte Biology and 
      Neurodegeneration (MEvS), and Neuropsychiatric Disorders (DFS), Netherlands 
      Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts 
      and Sciences, Amsterdam, The Netherlands.
FAU - van Eden, Corbert G
AU  - van Eden CG
FAU - Schuurman, Karianne
AU  - Schuurman K
FAU - van Strien, Miriam E
AU  - van Strien ME
FAU - Swaab, Dick F
AU  - Swaab DF
FAU - Huitinga, Inge
AU  - Huitinga I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (Cytokines)
RN  - 0 (Estrogens)
RN  - 0 (Receptors, Estrogen)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - EC 1.14.14.1 (Aromatase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Aromatase/metabolism
MH  - Brain/drug effects/*metabolism
MH  - Cytokines/genetics/metabolism
MH  - Estrogens/genetics/*metabolism
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*pathology
MH  - Nerve Fibers, Myelinated/metabolism/pathology
MH  - Postmortem Changes
MH  - Progesterone/genetics/*metabolism
MH  - Receptors, Estrogen/genetics/metabolism
MH  - *Sex Characteristics
MH  - Signal Transduction/drug effects/*physiology
EDAT- 2014/01/16 06:00
MHDA- 2014/03/14 06:00
CRDT- 2014/01/16 06:00
PHST- 2014/01/16 06:00 [entrez]
PHST- 2014/01/16 06:00 [pubmed]
PHST- 2014/03/14 06:00 [medline]
AID - 00005072-201402000-00004 [pii]
AID - 10.1097/NEN.0000000000000037 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2014 Feb;73(2):123-35. doi: 
      10.1097/NEN.0000000000000037.