| Summary: | This thesis describes the partial cloning of a mouse 11β-HSD2 cDNA which was used to generate riboprobes for determining 11β-HSD2 mRNA expression in the adult mouse brain by in situ hybridisation. Comparison with 11β-HSD2 distribution in the adult rat brain revealed distinct species differences; in the mouse, expression was found exclusively in the nucleus of the solitary tract (NTS), whilst the rat brain showed additional 11β-HSD2 expression in the subcommissural organ (SCO), the ventromedial nucleus of the hypothalamus (VMN) and the amygdala. MR in these regions are thought to mediate the central actions of aldosterone on blood pressure, cardiovascular function and salt appetite, suggesting 11β-HSD2 may be the mechanism by which these MR remain aldosterone-selective. The rat displays a marked need-free salt appetite and also readily consumes salt solutions when rendered sodium deficient by adrenalectomy or mineralocorticoid treatment. This behaviour is not seen in the mouse, however, and may account for the reduced 11β-HSD2 expression in its brain. Expression of 11β-HSD2 in rat brain was also examined following manipulation of salt balance by providing animals with a high or low salt diet for 14 days. Expression in the SCO was not affected by this regime, suggesting 11β-HSD is not a variable component of the SCO-adrenal negative feed-back loop. 11β-HSD2 was also suited in the neonatal rat brain where widespread expression was seen across the thalamus and external granular layer of the cerebellum, both areas associated with continued postnatal neuronal development. 11β-HSD bioactivity was initially high but fell away during the third postnatal week, correlating well with the pattern of mRNA expression.
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