The enzyme 5α-reductase 1 is the rate limiting step in A-ring reduction of glucocorticoids, and also metabolises other steroid hormones. 5α-reductase 1 is localised in metabolically active tissues, such as liver and fat, where it can therefore alter steroid metabolite profile.
We have recently demonstrated that whole body disruption of 5α-reductase, by either transgenic manipulation or pharmacological inhibition, results in the development of metabolic risk factors such as loss of insulin sensitivity and accumulation of liver fat.
We are now working towards defining the systems involved in effecting these metabolic outcomes.
5α-reductase is also expressed in the brain, where, in addition to catalysing glucocorticoid metabolism, it controls production of neuro-steroids.
We are currently determining the central effects of disrupted 5α-reductase in terms of metabolism and behaviour.