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Androgen-mediated immune function is altered by the apolipoprotein E gene.

Publication ,  Journal Article
Brown, CM; Xu, Q; Okhubo, N; Vitek, MP; Colton, CA
Published in: Endocrinology
July 2007

Androgens, like estrogens, have been linked to neuroprotective effects in the brain and to the improvement of cognitive function. Part of this effect may be due to the action of androgens on the innate immune response. We have examined the action of dihydrotestosterone (DHT) and testosterone on immune activation in primary cultures of microglia, the central nervous system macrophage. Our data indicate that DHT acts as an antiinflammatory agent and depresses both nitric oxide and TNFalpha production in a dose-dependent fashion. However, testosterone treatment of microglia and peritoneal macrophages increased supernatant nitrite levels, indicative of a proinflammatory effect. Because the apolipoprotein E (APOE) genotype also dramatically impacts macrophage function and has been linked to neurodegenerative disease, we compared the effects of APOE genotype on androgen-mediated regulation of inflammation using targeted replacement mice expressing only the human APOE3 or human APOE4 gene. Our data show that the antiinflammatory activity of DHT is significantly reduced in APOE4 targeted replacement mice compared to APOE3 mice. The effect was not due to an APOE isoform-specific change in androgen receptor mRNA and protein expression. Rather, innate immune signaling pathways regulated by androgens are altered in the APOE4 microglia. Compared to APOE3 microglia, DHT treatment did not reduce the phosphorylation of p38 MAPK or p54/p56 Janus kinase in APOE4 mice. Thus, our data suggest that DHT modulation of kinase activity is altered in microglia from mice expressing an APOE4 genotype and may impact androgen treatment therapies in individuals with an APOE4 genotype.

Duke Scholars

Published In

Endocrinology

DOI

ISSN

0013-7227

Publication Date

July 2007

Volume

148

Issue

7

Start / End Page

3383 / 3390

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Testosterone
  • Reverse Transcriptase Polymerase Chain Reaction
  • Phosphorylation
  • Nitrites
  • Nitric Oxide
  • Mitogen-Activated Protein Kinases
  • Microglia
  • Mice, Transgenic
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Brown, C. M., Xu, Q., Okhubo, N., Vitek, M. P., & Colton, C. A. (2007). Androgen-mediated immune function is altered by the apolipoprotein E gene. Endocrinology, 148(7), 3383–3390. https://doi.org/10.1210/en.2006-1200
Brown, Candice M., Qing Xu, Nobutaka Okhubo, Michael P. Vitek, and Carol A. Colton. “Androgen-mediated immune function is altered by the apolipoprotein E gene.Endocrinology 148, no. 7 (July 2007): 3383–90. https://doi.org/10.1210/en.2006-1200.
Brown CM, Xu Q, Okhubo N, Vitek MP, Colton CA. Androgen-mediated immune function is altered by the apolipoprotein E gene. Endocrinology. 2007 Jul;148(7):3383–90.
Brown, Candice M., et al. “Androgen-mediated immune function is altered by the apolipoprotein E gene.Endocrinology, vol. 148, no. 7, July 2007, pp. 3383–90. Pubmed, doi:10.1210/en.2006-1200.
Brown CM, Xu Q, Okhubo N, Vitek MP, Colton CA. Androgen-mediated immune function is altered by the apolipoprotein E gene. Endocrinology. 2007 Jul;148(7):3383–3390.
Journal cover image

Published In

Endocrinology

DOI

ISSN

0013-7227

Publication Date

July 2007

Volume

148

Issue

7

Start / End Page

3383 / 3390

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Testosterone
  • Reverse Transcriptase Polymerase Chain Reaction
  • Phosphorylation
  • Nitrites
  • Nitric Oxide
  • Mitogen-Activated Protein Kinases
  • Microglia
  • Mice, Transgenic
  • Mice