Androgen receptor mRNA expression in the human hippocampus

Beyenburg, Stefan; Watzka, Matthias; Clusmann, Hans; Blümcke, Ingmar; Bidlingmaier, F.; Elger, Christian E.; Stoffel‐Wagner, Birgit

doi:10.1016/s0304-3940(00)01542-1

Cited by 109 publications

(55 citation statements)

References 20 publications

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“…Nevertheless, such conversion may occur to a certain extent, which could explain why the effects of testosterone were overall weaker than those of estrogen, and also that the increase in divergent thinking was only relatively small in women showing the greatest increase in plasma testosterone concentration after this treatment. Androgen receptors that could mediate cognitive effects of testosterone have been identified in the hippocampus and the parietal cortex, although receptor expression in these regions is distinctly weaker than in the hypothalamus and amygdala showing highest androgen receptor density (Abdelgadir et al, 1999;Beyenburg et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Acute Influences of Estrogen and Testosterone on Divergent and Convergent Thinking in Postmenopausal Women

Krug

Mölle

Dodt

et al. 2003

Neuropsychopharmacol

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Previous studies indicated an enhanced capability of divergent creative thinking in young women during the ovulatory phase, which expressed itself also by an increased dimensional complexity of ongoing electroencephalographic (EEG) activity. Considering the enhanced plasma levels of estrogen and testosterone characterizing the ovulatory phase, we tested whether short-term administration of estrogen or testosterone in postmenopausal women with constantly low levels of gonadal steroids induces similar changes in divergent thinking. In two placebo-controlled cross-over studies, healthy postmenopausal women (n ¼ 12, in each study, mean age 58 years, range 47-65 years) were treated transdermally over 3 days with estrogen and testosterone, respectively, at doses inducing plasma hormone concentrations comparable with those observed in young women around ovulation. Capabilities of divergent thought and convergent analytical thought, performance on motor perseveration, and verbal memory were examined. EEG activity was recorded while subjects performed on tasks of thinking and during mental relaxation. Estrogen impaired divergent thinking (po0.01) and enhanced convergent thinking, motor perseveration, and memory for the initial word list (po0.05 for all tests). In parallel, EEG dimensional complexity was reduced (po0.05). Overall, these changes indicate an estrogen-induced shift from a 'divergent' towards a more 'convergent' mode of processing. However, overall less consistent, effects of testosterone were opposite to those of estrogen. It increased performance on some of the divergent thinking tasks (po0.05), and tended to increase EEG dimensional complexity during divergent thinking. Data indicate a differential sensitivity of modes of thinking to short-term treatment with estrogen and testosterone in postmenopausal women.

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Section: Discussionmentioning

confidence: 99%

Acute Influences of Estrogen and Testosterone on Divergent and Convergent Thinking in Postmenopausal Women

Krug

Mölle

Dodt

et al. 2003

Neuropsychopharmacol

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“…In relation to human behaviour, data from the MMAS showed that depression was significantly and inversely associated with total testosterone in men with shorter (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), but not with moderate and longer (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40), CAG repeats (56). Although we found that the length of the AR CAG repeat was not an effect modifier of the association between the hormones and the FC z-score, we cannot exclude the possibility that different relationships may exist with other cognitive domains.…”

Section: Previous Studies Of Ar Cag Repeat Length and Cognitive Functionmentioning

confidence: 99%

“…If endogenous androgens impact on cognitive function, it is possible that genetic variations such as the androgen receptor (AR) gene CAG repeat polymorphism may directly or indirectly modulate these relationships. ARs are widely distributed throughout the brain, including learning and memory critical regions such as the hippocampus (15) and cerebral cortex (16). Longer CAG repeat length in exon 1 of the X-linked AR gene has been associated with decreased androgen sensitivity, (17) and epidemiological and clinical studies have suggested that variability within the normal range of CAG repeat length modulates androgen action (18).…”

Section: Introductionmentioning

confidence: 99%

Endogenous hormones, androgen receptor CAG repeat length and fluid cognition in middle-aged and older men: results from the European Male Ageing Study

Lee

Ulubaev

Tajar

et al. 2010

European Journal of Endocrinology

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Objective: Data remain divergent regarding the activational effects of endogenous hormones on adult cognitive function. We examined the association between cognition, hormones and androgen receptor (AR) CAG repeat length in a large cohort of men. Design: Community-based, cross-sectional study of 3369 men aged 40-79 years. Methods: Cognition tests were the Rey-Osterrieth Complex Figure, Camden Topographical Recognition Memory and Digit-Symbol Substitution. A fluid cognition (FC) z-score was computed from the individual tests. Testosterone, oestradiol (OE 2 ) and 5a-dihydrotestosterone were measured by gas chromatography-mass spectrometry; DHEAS, LH, FSH and sex hormone-binding globulin (SHBG) by electrochemiluminescence. Free testosterone and OE 2 were calculated from total hormone, SHBG and albumin. CAG repeat lengths were assayed by PCR genotyping. Results: Total testosterone and free testosterone were associated with higher FC z-scores, LH and FSH with lower FC z-scores in age-adjusted linear regressions. After adjusting for health, lifestyle and centre, a modest association was only observed between DHEAS and a lower FC z-score (bZK0.011, PZ0.02), although this was driven by subjects with DHEAS levels O10 mmol/l. Locally weighted plots revealed no threshold effects between hormones and FC. There was no association between CAG repeat length and FC z-score after adjustment for age and centre (bZK0.007, PZ0.06), nor any interaction effect between CAG repeat length and hormones. Conclusion: Our results suggest that endogenous hormones are not associated with a vision-based measure of FC among healthy, community-dwelling men. Further studies are warranted to determine whether 'high' DHEAS levels are associated with poorer performance on a broader range of neuropsychological tests.

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“…11 The aim of the present study was to test for interactive effects of APOE genotype and testosterone on hippocampal volume in middleaged men. Along with being a primary site of AD neuropathology, 12 the hippocampus is rich in ARs, 13 making it vulnerable to the agerelated decline in testosterone levels. Extrapolating from previous animal models, 9,10 we hypothesized that an interaction between APOE genotype and testosterone would be present in humans such that being both ⑀4-positive and having low testosterone levels would be associated with smaller hippocampal volumes relative to other combinations of APOE genotype and testosterone level.…”

mentioning

confidence: 99%

Testosterone modifies the effect of APOE genotype on hippocampal volume in middle-aged men

Panizzon

Hauger²,

Dale³

et al. 2010

Neurology

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Androgen receptor mRNA expression in the human hippocampus

Cited by 109 publications

References 20 publications

Acute Influences of Estrogen and Testosterone on Divergent and Convergent Thinking in Postmenopausal Women

Acute Influences of Estrogen and Testosterone on Divergent and Convergent Thinking in Postmenopausal Women

Endogenous hormones, androgen receptor CAG repeat length and fluid cognition in middle-aged and older men: results from the European Male Ageing Study

Testosterone modifies the effect of APOE genotype on hippocampal volume in middle-aged men

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