Aromatase P45019

Of all the steroidogenic P450s, P45019 is the best studied. Its catalytic activity in the brain has been known since 1975 (1) and has been measured in several laboratories over the past years (42-46). Today the enzyme, its mRNA, and its catalytic activity have been localized in the rat brain. Immunohistochemical studies revealed that P45019 is localized in neurons in the amygdala and supraoptic nucleus, regions high in aromatase activity (46). In addition, several brain regions not previously known to contain the enzyme were positively stained. These included the reticular thalamic nucleus, the olfactory tract, and the piriform cortex. From studies conducted in several laboratories two very interesting pieces of information about brain P45019 have emerged that may help to clarify some of the puzzling information about other brain P450s. These are:

1. A significant part of the regulation of the enzyme is post-transcriptional. As will be evident at the end of this chapter, many P450s in the brain appear to be regulated post-transcriptionally, although this phenomenon is not as clearly documented with other P450s as it has been for P45019. The mechanisms involved in such regulation need to be examined. It may well be that increase in translatability or stabilization of protein is a mechanism used by the brain to rapidly increase the amounts of enzyme. The use of post transcriptional mechanisms in the brain means that the relationship between mRNA and corresponding protein is not constant. This could be part of the explanation for the lower than expected levels of mRNA in certain brain regions where the protein levels are relatively high.

2. P45019 may be localized at nerve terminals (46). Such a localization strongly indicates a role in neurotransmission or neuromodulation. It also means that there will be differences in the localization of the mRNAs, which should be confined to the cell body, and the protein, which could be in the terminals far away from the cell body.

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