Ontogeny of the neurosteroid enzyme Cyp7b in the mouse

The function of the major adrenal steroid dehydroepiandrosterone (DHEA) is not known. It has been reported to improve learning and memory in mice and can exert neuroprotective and trophic effects, particularly in the hippocampus. We recently described a cytochrome P450 (Cyp7b), that catalyses the 7alpha-hydroxylation of DHEA and related steroids and sterols. In this paper, we have used mRNA in situ hybridisation to map the ontogeny of cyp7b in the foetal and adult mouse. Cyp7b mRNA is highly expressed throughout from embryonal (E) day 12.5 (the earliest day studied). There is also expression throughout the body, including the spine, thymus, developing kidneys, lungs and urogenital region. Widespread expression becomes more restricted towards birth: in newborn mice expression is largely limited to the hippocampus, with some expression being detected in kidney. The overall decline in mRNA, and increasing restriction to the hippocampus, is reflected in the DHEA hydroxylation activity of brain homogenates. This pattern of cyp7b mRNA expression in specific organs could be consistent with a protective role in foetal development, with highest expression seen when the foetus is most vulnerable to steroid excess (i.e.) early gestation.