ABSTRACT
The exploding field of neurosteroid research, conducted both at basic and clinical levels, was created on the base of two lines of discoveries from the 1980s. The group of Corpechot, Baulieu and Robel reported the existence of steroidogenesis in the Central Nervous System (Corpechot et al., 1981, 1983; Baulieu et al., 1987) and created the term of “neurosteroids”, and independently Harrison with Simmons and I discovered steroid interaction with neurotransmitter receptors. Our discoveries derived from two different experimental approaches. My finding originated from biochemical observation that cholesterol, used originally as a modifier of membrane fluidity, altered ligand binding to brain GABAA receptors. It culminated in the report describing modulation of brain GABA receptors by pregnenolone sulfate and some corticosteroids (Majewska et al., 1985). On the other hand, Harrison and Simmons found steroid modulation on GABA receptor complex while studying the electrophysiological effects of the steroidal anesthetic, alphaxalone (Harrison and Simmons, 1984). Subsequently, while working together with Harrison at the National Institutes of Health, we made further discoveries employing combined neurochemical and electrophysiological techniques. We described potent barbiturate-like properties of reduced metabolites of progesterone and deoxycorticosterone (Majewska et al., 1986) and determined structure-function relationships of agonistic steroid interactions with GABAA receptors (Harrison et al., 1987).
