EXPRESSION OF STEROID SULFATASE DURING EMBRYOGENESIS

Neurosteroids are steroids that are synthesized de novo in the brain f rom cholesterol and, in general, mediate their effects through ion-gat ed channel receptors such as gamma-aminobutyric acid(A) (GABA(A)) and N-methyl-D-aspartate receptors rather than through classical nuclear s teroid hormone receptors. Steroid hormones are known to exist not only as free compounds, but also as sulfated derivatives. Pharmacological studies indicate that unconjugated and sulfated steroids, such as preg nenolone and pregnenolone sulfate, may have opposite effects on GABA(A ) receptors. Thus, pregnenolone acts as a potent positive allosteric m odulator of gamma-aminobutyric acid action at GABA(A) receptors, where as pregnenolone sulfate acts as a potent negative modulator. Recent ex periments also suggest that dehydroepiandrosterone and dehydroepiandro sterone sulfate may have distinct effects on growth of neurites from e mbryonic neocortical neurons in vitro. Thus, regulation of steroid sul fation may have profound behavioral and morphological effects on the n ervous system. We, therefore, studied the developmental expression of the enzyme steroid sulfatase (STS), which converts sulfated steroids t o free steroids. By in situ hybridization, STS messenger RNA was expre ssed in the embryonic mouse cortex, hindbrain, and thalamus during the last third of gestation. The sites of expression of STS were similar ta those of P450c17, suggesting that these two enzymes may have concer ted actions in similar functional processes.