[Neurosteroid dehydroepiandrosterone and brain function].

Area of Science:

• Neuroendocrinology
• Neurobiology
• Steroid biochemistry

Context:

• Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) are synthesized de novo in the brain, termed neurosteroids.
• Brain-synthesized steroids play crucial roles in neurological functions.
• DHEA(S) metabolism occurs in peripheral tissues like adipose tissue, yielding active metabolites such as estradiol and testosterone.

Purpose:

• To review the biosynthesis, metabolism, and neurobiological functions of DHEA(S).
• To analyze the enzymatic roles of sulfatase and sulfotransferase in DHEA(S) interconversion.
• To explore the clinical applications of DHEA(S) in neurological disorders.

Summary:

• DHEA(S) synthesis pathways differ between primate and other animal adrenal glands.
• Mechanisms of DHEAS entry into the brain include conversion to DHEA and direct passage through unprotected brain regions.
• Neurobiological effects of DHEA(S) encompass neuroprotection, neurogenesis, neuronal survival, apoptosis modulation, and catecholamine regulation.

Impact:

• DHEA(S) demonstrates neuroprotective, antioxidant, anti-inflammatory, and anti-glucocorticoid properties.
• DHEA(S) holds potential therapeutic value for Alzheimer's disease, cognitive dysfunction, and other central nervous system disorders.
• Understanding neurosteroid functions advances therapeutic strategies for neurological conditions.