Therapeutic implications of brain steroidogenesis

Abstract

AbstractThe nervous system is a steroidogenic tissue and several steroids synthesized locally in the brain, such as pregnenolone, progesterone and estradiol, modulate neuronal and glial physiology and are neuroprotective. The brain upregulates steroidogenesis at sites of injury as part of a program triggered by neural tissue to cope with neurodegenerative insults. Pharmacological targets to increase brain steroidogenesis and promote neuroprotection include the molecules that transport cholesterol to the inner mitochondrial membrane, where the first enzyme for steroidogenesis is located. Furthermore, the human gene encoding aromatase, the enzyme that synthesizes estradiol, is under the control of different tissue-specific promoters, and it is therefore conceivable that selective aromatase modulators can be developed that will enhance the expression of the enzyme and the consequent increase in estrogen formation in the brain but not in other tissues.