Androgen Receptor In Hippocampus Research Articles

Down, But Not Out: Partial Elimination of Androgen Receptors in the Male Mouse Brain Does Not Affect Androgenic Regulation of Anxiety or HPA Activity.

We previously found that androgen receptor (AR) activity mediates two effects of T in adult male mice: reduction of anxiety-like behaviors and dampening of the hypothalamic-pituitary-adrenal response to stress. To determine whether brain ARs mediate these effects, we used the Cre/loxP technology seeking to disable AR throughout the central nervous system (CNS). Female mice carrying the floxed AR allele (ARlox) were crossed with males carrying cre recombinase transgene controlled by the nestin promoter (NesCre), producing cre in developing neurons and glia. Among male offspring, four genotypes resulted: males carrying ARlox and NesCre (NesARko), and three control groups (wild types, NesCre, and ARlox). Reporter mice indicated ubiquitous Cre expression throughout the CNS. Nevertheless, AR immunocytochemistry in NesARko mice revealed efficient knockout (KO) of AR in some brain regions (hippocampus and medial prefrontal cortex [mPFC]), but not others. Substantial AR protein was seen in the amygdala and hypothalamus among other regions, whereas negligible AR remained in others like the bed nucleus of the stria terminalis and dorsal periaqueductal gray. This selective KO allowed for testing the role of AR in hippocampus and mPFC. Males were castrated and implanted with T at postnatal day 60 before testing on postnatal day 90-100. In contrast with males with global KO of AR, T still modulated anxiety-related behavior and hypothalamic-pituitary-adrenal activity in NesARko males. These results leave open the possibility that AR acting in the CNS mediates these effects of T, but demonstrate that AR is not required in the hippocampus or mPFC for T's anxiolytic effects.

Intrahippocampal Injection of 3α Diol (a Testosterone Metabolite ) and Indomethacin (3α-HSD Blocker), Impair Acquisition of Spatial Learning and Memory in Adult Male Rats.

Hippocampus is essentially involved in learning and memory processes, and is known to be a target for androgen actions. The high density of the androgen receptors in hippocampus shows that there must be some relationship between androgens and memory. Androgen effects on spatial memory are complex and contradictory. Some evidence suggests a positive correlation between androgens and spatial memory. While some other reports indicated an impairment effect. The present study was conducted to assess the effect of 3α diol on spatial discrimination of rats. Adult male rats were bilaterally cannulated into CA1 region of hippocampus and then received 3α diol (0.2, 1, 3 and 6 μg/ 0.5 μL/side), indomethacin (1.5, 3 and 6 μg/ 0.5 μL/side), indomethacin (3 μg/ 0.5 μL/side) + 3α diol (1μg/ 0.5 μL/side), 25-35 min before training in Morris Water Maze task. Our results showed that injection of 3α diol (1, 3 and 6 μg/ 0.5 μL/ side) and indomethacin (3 and 6 μg/ 0.5 μL/side) significantly increased the escape latency and traveled distance to find hidden platform. It is concluded that intra CA1 administration of 3α diol and indomethacin could impair spatial learning and memory in acquisition stage. However, intra hippocampal injection of indomethacin plus 3α diol could not change spatial learning and memory impairment effect of indomethacin or 3α diol in Morris Water Maze task.

Anti‐epileptic drug phenytoin enhances androgen metabolism and androgen receptor expression in murine hippocampus

Epilepsy is very often related to strong impairment of neuronal networks, particularly in the hippocampus. Previous studies of brain tissue have demonstrated that long-term administration of the anti-epileptic drug (AED) phenytoin leads to enhanced metabolism of testosterone mediated by cytochrome P450 (CYP) isoforms. Thus, we speculate that AEDs affect androgen signalling in the hippocampus. In the present study, we investigated how the AED phenytoin influences the levels of testosterone, 17beta-oestradiol, and androgen receptor (AR) in the hippocampus of male C57Bl/6J mice. Phenytoin administration led to a 61.24% decreased hippocampal testosterone level as compared with controls, while serum levels were slightly enhanced. 17beta-Oestradiol serum level was elevated 2.6-fold. Concomitantly, the testosterone metabolizing CYP isoforms CYP3A11 and CYP19 (aromatase) have been found to be induced 2.4- and 4.2-fold, respectively. CYP3A-mediated depletion of testosterone-forming 2beta-, and 6beta-hydroxytestosterone was significantly enhanced. Additionally, AR expression was increased 2-fold (mRNA) and 1.8-fold (protein), predominantly in the CA1 region. AR was shown to concentrate in nuclei of CA1 pyramidal neurons. We conclude that phenytoin affects testosterone metabolism via induction of CYP isoforms. The increased metabolism of testosterone leading to augmented androgen metabolite formation most likely led to enhanced expression of CYP19 and AR in hippocampus. Phenytoin obviously modulates the androgen signalling in the hippocampus.