In the rat hippocampus, corticosteroids modulate neuronal excitability. Glucocorticoid excess within the rat hippocampus results in a neurodegenerative effect, although corticosteroids also protect oligodendrocytes from cytokine-mediated apoptosis. Other studies have shown that systemically insignificant levels of aldosterone affect systemic blood pressure when administered icv. Previously, we have shown by RT-PCR and immunohistochemistry that the genes for 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) are expressed within the rat hippocampus and cerebellum. Here we show for the first time that transcription of the CYP11B1 and CYP11B2 genes occurs in human cerebellum and hippocampus.
For this study, we used commercially-available human cDNA derived from pooled poly-A RNA samples. We demonstrated the presence, at low concentrations, of CYP11B1 and CYP11B2 transcripts in human cerebellum and hippocampus using PCR followed by Southern blotting. In addition, transcripts coding for the side-chain cleavage enzyme, the Steroidogenic Acute Regulatory protein (StAR) and 21-hydroxylase were also found to be present, suggesting that all the machinery required for the de novo production of cortisol and aldosterone from cholesterol is present in these brain regions.
Concurrent studies by another group failed to detect CYP11B1 and CYP11B2 in human cerebellum or hippocampus. They used commercially-available RNA rather than cDNA, so the low levels of relevant transcripts may have degraded before they could perform reverse transcription.
03 - 04 Dec 2001
Society for Endocrinology