Related Experiment Video
Updated: Jul 16, 2026
08:20
A Hyperandrogenic Mouse Model to Study Polycystic Ovary Syndrome
Published on: October 2, 2018
Androgen-mediated immune function is altered by the apolipoprotein E gene
Candice M Brown1, Qing Xu, Nobutaka Okhubo
1Division of Neurology, Duke University Medical Center, Box 2900, Durham, North Carolina 27710, USA.
Endocrinology
|March 31, 2007
Summary
Dihydrotestosterone (DHT) shows anti-inflammatory effects on brain immune cells, but this is reduced in individuals with the APOE4 gene. This finding impacts potential androgen therapies for neurodegenerative diseases.
Area of Science:
- Neuroimmunology
- Endocrinology
Background:
- Androgens, similar to estrogens, are associated with neuroprotection and improved cognitive function.
- Androgen effects on the central nervous system (CNS) may involve modulation of the innate immune response.
Purpose of the Study:
- To investigate the effects of dihydrotestosterone (DHT) and testosterone on immune activation in microglia.
- To examine the influence of apolipoprotein E (APOE) genotype on androgen-mediated immune regulation in the CNS.
Main Methods:
- Primary cultures of microglia (CNS macrophages) were treated with DHT and testosterone.
- Targeted replacement mice expressing human APOE3 or APOE4 genes were used to compare androgen effects.
- Analysis included nitric oxide and TNF-alpha production, and phosphorylation of p38 MAPK and Janus kinase.
Main Results:
- DHT demonstrated dose-dependent anti-inflammatory effects, reducing nitric oxide and TNF-alpha production.
- Testosterone exhibited pro-inflammatory effects on microglia and peritoneal macrophages.
- The anti-inflammatory activity of DHT was significantly diminished in APOE4 targeted replacement mice compared to APOE3 mice.
- DHT's modulation of p38 MAPK and Janus kinase phosphorylation was impaired in APOE4 microglia.
Conclusions:
- DHT acts as an anti-inflammatory agent in microglia, but its efficacy is reduced in the presence of the APOE4 genotype.
- Altered innate immune signaling pathways in APOE4 microglia may explain the reduced DHT effect.
- These findings suggest that APOE genotype could influence the effectiveness of androgen-based therapies for neurological conditions.
More Related Videos
07:36Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
09:38Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
Related Concept Videos
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
02:32Exon Recombination
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Exon shuffling follows “splice frame rules.” Each exon has three reading...
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
01:28Diversity of Antigen Receptors
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
02:23RNA Editing
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
01:09Epistasis Analysis
Although Mendel chose seven unrelated traits in peas to study gene segregation, most traits involve multiple gene interactions that create a spectrum of phenotypes. When the interaction of various genes or alleles at different locations influences a phenotype, this is called epistasis. Epistasis often involves one gene masking or interfering with the expression of another (antagonistic epistasis). Epistasis often occurs when different genes are part of the same biochemical pathway. The...