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Steroid hydroxylase gene expression is multifactorial in nature, being regulated by tissue-specific, developmental, constitutive and signal transduction systems. The biochemistry of this complex pattern of regulation is not yet clearly elucidated, but studies in several laboratories have led to an understanding of specific aspects of regulation, particularly that involving signal transduction. The complexity of regulation appears to be necessary for normal human physiology because of the wide variety of steroid hormones produced by these enzymes. Genetic diseases associated with the steroid hydroxylases provide examples of how aberrant physiology can result from alterations in the multifactorial regulation of steroid hydroxylase gene expression.