O impacto dos hormônios andrógenos no cérebro

Abstract

Androgenic hormones (HAs) are steroids that play a fundamental role in sexual dimorphism, the development of sexual characteristics and spermatogenesis. They include dehydroepiandrosterone (DHEA), its sulphate (DHEAS), androstenedione (AD), testosterone (TTT), dihydrotestosterone (DHT) and are produced in the adrenal gland, testes and ovaries through the action of various enzymes. The mechanism of action of these hormones occurs predominantly through the activation of the androgen receptor (AR). Evidence suggests that AHs also influence the maintenance of homeostasis in the central nervous system (CNS), although the mechanisms underlying these effects are not yet fully elucidated in the literature. Accordingly, the present study aims to investigate the impact of AHs on brain function. Studies indicate that AHs can act through the activation of ARs, which are widely distributed throughout the CNS in various species. Their effects include modulation of brain development, promoting sexual differentiation of the brain during fetal and postnatal stages, as well as regulation of neural circuits associated with social communication and inhibitory profiles of GABA. The role of AHs in neuroplasticity has also been demonstrated, particularly through alterations in dendritic spine morphology mediated by rapid, non-genomic signaling pathways such as ERK1/2-CREB, PKC, and LIMK. Another relevant aspect is the neuroprotective effect attributed to androgens, including anti-apoptotic, antiinflammatory, and antioxidant properties. Additionally, AHs have been implicated in the modulation of pathological processes associated with Alzheimer’s disease (AD), promoting the reduction of β-amyloid plaque accumulation and Tau hyperphosphorylation following hormonal exposure. These steroids also influence behavior and cognition by exerting negative feedback on the hypothalamic–pituitary–adrenal (HPA) axis, thereby reducing stress and anxiety responses. Positive effects on learning and memory have likewise been reported. Thus, reduced levels of these hormones, whether due to aging or androgen deprivation therapies, may impair cognitive functions. In contrast, supraphysiological exposure to exogenous androgens has been associated with increased anxiety, stress, and aggressive behavior. Finally, given the neuroprotective and cognitive benefits of AHs, selective androgen receptor modulators (SARMs) and analogs such as BNN27 have been investigated for their therapeutic potential in the CNS. These findingsunderscore the relevance of further research on the central effects of androgens and their clinical applications in neurodegenerative and neuropsychiatric contexts