Sexual differentiation of the brain in man and animals: Of relevance to Klinefelter syndrome?

McCarthy, Margaret M.

doi:10.1002/ajmg.c.31351

Cited by 10 publications

(5 citation statements)

References 91 publications

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“…In rodents, masculinization remarkably involves aromatase of testosterone to estradiol and subsequent effects on estrogen receptors. In humans, more straightforwardly, the androgen receptors seem to underlie masculinization and, as we propose, also impairments in cognitive empathy3536.…”

Section: Discussionmentioning

confidence: 60%

Testosterone Administration Moderates Effect of Social Environment on Trust in Women Depending on Second-to-Fourth Digit Ratio

Buskens

Raub

Miltenburg

et al. 2016

Sci Rep

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Animal research has established that effects of hormones on social behaviour depend on characteristics of both individual and environment. Insight from research on humans into this interdependence is limited, though. Specifically, hardly any prior testosterone experiments in humans scrutinized the interdependency of testosterone with the social environment. Nonetheless, recent testosterone administration studies in humans repeatedly show that a proxy for individuals’ prenatal testosterone-to-estradiol ratio, second-to-fourth digit-ratio (2D:4D ratio), influences effects of testosterone administration on human social behaviour. Here, we systematically vary the characteristics of the social environment and show that, depending on prenatal sex hormone priming, testosterone administration in women moderates the effect of the social environment on trust. We use the economic trust game and compare one-shot games modelling trust problems in relations between strangers with repeated games modelling trust problems in ongoing relations between partners. As expected, subjects are more trustful in repeated than in one-shot games. In subjects prenatally relatively highly primed by testosterone, however, this effect disappears after testosterone administration. We argue that impairments in cognitive empathy may reduce the repeated game effect on trust after testosterone administration in subjects with relatively high prenatal testosterone exposure and propose a neurobiological explanation for this effect.

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Section: Discussionmentioning

confidence: 60%

Testosterone Administration Moderates Effect of Social Environment on Trust in Women Depending on Second-to-Fourth Digit Ratio

Buskens

Raub

Miltenburg

et al. 2016

Sci Rep

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“…In primates, testosterone typically influences behavior via binding to androgen receptors (ARs) and modulating downstream physiological processes (reviewed in McCarthy, 2013). If testosterone-induced aggression is AR dependent, polymorphisms that influence the efficiency of this androgenic pathway-through impairing or bolstering gene transcription or other, nongenomic effects-should directly moderate the effects of testosterone (and also testosterone-personality interactions) on aggression.…”

mentioning

confidence: 99%

Using a Psychopharmacogenetic Approach To Identify the Pathways Through Which—and the People for Whom—Testosterone Promotes Aggression

et al. 2019

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Little is known about the neurobiological pathways through which testosterone promotes aggression or about the people in whom this effect is observed. Using a psychopharmacogenetic approach, we found that testosterone increases aggression in men ( N = 308) with select personality profiles and that these effects are further enhanced among those with fewer cytosine-adenine-guanine (CAG) repeats in exon 1 of the androgen receptor (AR) gene, a polymorphism associated with increased AR efficiency. Testosterone’s effects were rapid (~30 min after administration) and mediated, in part, by subjective reward associated with aggression. Testosterone thus appears to promote human aggression through an AR-related mechanism and to have stronger effects in men with the select personality profiles because it more strongly upregulates the subjective pleasure they derive from aggression. Given other evidence that testosterone regulates reward through dopaminergic pathways, and that the sensitivity of such pathways is enhanced among individuals with the personality profiles we identified, our findings may also implicate dopaminergic processes in testosterone’s heterogeneous effects on aggression.

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“…At this developmental stage, testosterone synthesis by male gonads, and its estrogenic conversion by brain aromatase are responsible for brain masculinization in males that "organizes" neural circuitries and neurons persisting for the entire life to react to circulating or locally produced steroids in a male-specific manner. This process is associated to a sexually-specific expression of sex hormone receptors in numerous brain areas (3,320). The sexual differentiation involves all neural cells: in adult brains, astrocytes show a clear sexual dimorphism (321)(322)(323) in their morphology (primary process length and number distribution) (324)(325)(326), differentiation and function (327)(328)(329)(330).…”

Section: B the Essential Role Of Sex Steroids In Brain Sexual Differe...mentioning

confidence: 99%

The Role of Sex and Sex Hormones in Neurodegenerative Diseases

et al. 2019

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Neurodegenerative diseases (NDs) are a wide class of disorders of the central nervous system (CNS) with unknown etiology. Several factors were hypothesized to be involved in the pathogenesis of these diseases, including genetic and environmental factors. Many of these diseases show a sex prevalence and sex steroids were shown to have a role in the progression of specific forms of neurodegeneration. Estrogens were reported to be neuroprotective through their action on cognate nuclear and membrane receptors, while adverse effects of male hormones have been described on neuronal cells, although some data also suggest neuroprotective activities. The response of the CNS to sex steroids is a complex and integrated process that depends on (i) the type and amount of the cognate steroid receptor and (ii) the target cell type—either neurons, glia, or microglia. Moreover, the levels of sex steroids in the CNS fluctuate due to gonadal activities and to local metabolism and synthesis. Importantly, biochemical processes involved in the pathogenesis of NDs are increasingly being recognized as different between the two sexes and as influenced by sex steroids. The aim of this review is to present current state-of-the-art understanding on the potential role of sex steroids and their receptors on the onset and progression of major neurodegenerative disorders, namely, Alzheimer’s disease, Parkinson’s diseases, amyotrophic lateral sclerosis, and the peculiar motoneuron disease spinal and bulbar muscular atrophy, in which hormonal therapy is potentially useful as disease modifier.

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Sexual differentiation of the brain in man and animals: Of relevance to Klinefelter syndrome?

Cited by 10 publications

References 91 publications

Testosterone Administration Moderates Effect of Social Environment on Trust in Women Depending on Second-to-Fourth Digit Ratio

Testosterone Administration Moderates Effect of Social Environment on Trust in Women Depending on Second-to-Fourth Digit Ratio

Using a Psychopharmacogenetic Approach To Identify the Pathways Through Which—and the People for Whom—Testosterone Promotes Aggression

The Role of Sex and Sex Hormones in Neurodegenerative Diseases

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