Androgen receptors (AR) in the brain are intracellular proteins that bind to and mediate the effects of androgenic hormones, primarily testosterone and its potent metabolite, dihydrotestosterone (DHT). These receptors are widely distributed throughout various cerebral regions, including the hippocampus, hypothalamus, and cortex, indicating a broad neuroregulatory role. Their presence signifies a direct pathway through which androgens influence neuroendocrine function, mood regulation, cognitive performance, and neuroprotection. The function of these receptors is critical for maintaining central nervous system homeostasis across the lifespan in both males and females.
Origin
The identification of androgen receptors is a fundamental achievement in molecular endocrinology, with their specific localization in the brain being established through immunohistochemical and molecular biology techniques. The term’s origin is rooted in the discovery of steroid hormone action, where hormones must bind to a specific receptor to exert their effects on gene transcription. This understanding expanded the traditional view of androgens as solely reproductive hormones to include their profound neuroregulatory roles. The presence of AR in the brain underscores the interconnectedness of the endocrine and nervous systems.
Mechanism
Upon binding to an androgen, the AR undergoes a conformational change, translocates from the cytoplasm into the cell nucleus, and acts as a ligand-activated transcription factor. This complex then binds to specific DNA sequences, known as Androgen Response Elements (AREs), to regulate the transcription of target genes. The resulting gene expression changes influence neuronal development, synaptic plasticity, and the synthesis of neurotransmitters and neurotrophic factors. Androgen signaling in the brain modulates pathways crucial for memory consolidation, spatial cognition, and emotional resilience.
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