Neurosteroids in Biological Rhythms and Stress

Plasma levels of adrenal steroids typically undergo diurnal cyclical changes (72). Likewise, there are circadian variations in the brain concentrations of neurosteroids (73). In the brain of the nocturnal animal rat, DHEAS levels peak at the prenocturnal hours and remain high through the first half of the dark cycle (73), following the plasma pattern. In humans, DHEAS in plasma manifests modest circadian rhythms and its higher levels are generally found during day hours and lower at night (73,74). The brain levels of DHEAS in humans may undergo similar diurnal changes as the plasma levels. The elevated concentrations of DHEAS and other excitatory steroids may serve an analeptic role during periods of intense activity.

The pioneering work of Selye (75) delineated the essential role of adrenal steroids during stress. Concentrations of GABA antagonistic neurosteroids, PREGS, and DHEAS are also elevated in the brain during stress (1), thus increasing neuronal arousal. On the other hand, increased synthesis of the GABA-agonistic steroid 3a,5a-THDOC, may calm the brain during stress. Hence the relative ratios of excitatory to inhibitory neurosteroids may determine to some extend the individual's behavior during stress. Complex role of neurosteroids in stress was discussed in detail elsewhere (2).

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