Johannes D. Veldhuis, MD


March 15, 2000

In This Article

Adrenopause: The Role of DHEA or DHEA-S in Aging

The enzymic machinery of the adrenal zona reticularis fails in aging men and women. However, the ability of the zona fasciculata to produce cortisol is preserved (based on ACTH infusion, insulin tolerance, and metyrapone testing). Mineralocorticoid and glucocorticoid receptors in the hippocampus are variably downregulated in aging humans. Excessive lifelong adrenal cortisol feedback on the brain may exacerbate the aging-associated loss in neuronal synapses and plasticity.

Extraglandular neurosteroids (typically progestin derivatives) produced by CNS astroglia regulate the activity of neuronal ion-channels (eg, via GABA-A receptors). The mechanisms by which neurosteroids interact with corticosteroids to modulate the cognitive and affective changes of aging have not been described.