Neuroactive steroids in periphery and cerebrospinal fluid

Abstract Some peripheral steroids penetrate the blood-brain barrier (BBB), providing at least substances for the CNS steroid metabolome. That is why the predictive value of the peripheral steroids appears to be comparable with that of the cerebrospinal fluid (CSF) steroids. The concentrations of the CSF steroids are pronouncedly lower in comparison with the ones in circulation. The available data indicate that the levels of pregnenolone sulfate substantially increase in the rat brain tissue after the administration of pregnenolone into the circulation. In the human circulation there are about two orders of magnitude higher levels of pregnenolone sulfate compared to the free pregnenolone. Our data show insignificant correlation between CSF and serum pregnenolone, but a borderline one between CSF pregnenolone and serum pregnenolone sulfate. Therefore in humans, the circulating pregnenolone sulfate might be of an importance for pregnenolone concentration in the CNS. In contrast to free pregnenolone, dehydroepiandrosterone (DHEA) in the CSF correlates with both unconjugated and conjugated DHEA in the serum. These data as well as the low C17-hydroxylase-C17,20-lyase activity in the CNS might indicate that DHEA levels in the CNS are influenced by peripheral levels of DHEA and its sulfate. According to the information, available part of the neurosteroids may be synthesized de novo in the CNS, but substantial part of the steroid metabolites may be also synthesized in the CNS from the steroid precursors or directly transported through BBB from the periphery. The processes mentioned above may be complimentary in some cases. Brain synthesis may provide minimal level of neurosteroids, which are indispensable for the CNS functions. Thus, brain steroids of peripheral origin may reflect various physiological situations or even pathologies. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.