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 call exert neuroprotective and trophic effects, particularly in the hippoca mpus. We recently described a cytochrome P450 (Cyp7b), that catalyses the 7 alpha -hydroxylation of DHEA and related steroids and sterols. In this pap er, we have used rrRNA in situ hybridisation to map the ontogeny of cyp7b i n the foetal and adult mouse. Cyp7b mRNA is highly expressed throughout hom embryonal (E) day 12.5 (the earliest day studied). There is also expressio n throughout the body, including the spine, thymus, developing kidneys, lun gs and urogenital region. Widespread expression becomes more restricted tow ards birth: in newborn mice expression is largely limited to the hippocampu s: with some expression being detected in kidney. The overall decline in mR NA, and increasing restriction to the hippocampus, is reflected in the DHEA hydroxylation activity of brain homogenates. This pattern of cyp7b mRNA ex pression in specific organs could be consistent with a protective role in f oetal development, with highest expression seen when the foetus is most vul nerable to steroid excess (i.e.) early gestation. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.