Chapter Five: Steroidogenic enzymes in the hippocampus: Transcriptional regulation aspects. Hormones, Regulators and Hippocampus.

ROSSETTI MF; VARAYOUD J; RAMOS JG

Vitamins and Hormones.

Elsevier

Año: 2022; p. 171 - 189

Neurosteroids are steroids synthesized de novo from cholesterol in brain regions, and regulate processes associated with the development and functioning of the nervous system. Enzymes and proteins involved in the synthesis of these steroids have been detected in several brain regions, including hippocampus, hypothalamus, and cerebral cortex. Hippocampus has long been associated with learning and memory functions, while the loss of its functionality has been linked to neurodegenerative pathologies. In this sense, neurosteroids are critical for the maintenance of hippocampal functions and neuroprotective effects. Moreover, several factors have been shown to deregulate expression of steroidogenic enzymes in the rodent brain, including aging, enrichment experiences, diet habits, drug/alcohol consumption, hormone fluctuations, neurodegenerative processes and other diseases. These transcriptional deregulations are mediated mainly by transcription factors and epigenetic mechanisms. An epigenetic modification of chromatin involves changes in bases and associated proteins in the absence of changes in the DNA sequence. One of the most well-studied mechanisms related to gene silencing is DNA methylation, which involves a reversible addition of methyl groups in a cytosine base. Importantly, these epigenetic marks could be maintained over time and could be transmitted transgenerationally. The aim of this chapter is to present the most relevant steroidogenic enzymes described in rodent hippocampus; to discuss about their transcriptional regulation under different conditions; to show the main gene control regions and to propose DNA methylation as an epigenetic mechanism through which the expression of these enzymes could be controlled.