Abstract
Although circulating plasma concentrations of androgens are determined in pan by peripheral interconversion in a variety of non-endocrine tissues, the role of the gastrointestinal tract in the peripheral metabolism of testosterone has not been established. Oxidation of testosterone to androstenedione was the predominant conversion by homogenates of rat and human small intestinal mucosa. Reduction of testosterone was not observed. The conversion of testosterone to androstenedione was independent of intestinal bacteria since it was effected by homogenates of germ-free rat jejunal mucosa. The conversion conformed to the kinetics of an enzyme-mediated reaction, with an apparent Michaelis constant for testosterone of 2.8 × 10 −6 M. Assay conditions for the enzyme responsible for this conversion, 17β-hydroxysteroid dehydrogenase (17β-HSD; E.C. 1.1.1.51) were determined. Specific activity of 17β-HSD in the intestinal mucosa was similar to testis and lung but greater than skeletal muscle or ventral prostate. The estimated total 17β-HSD capacity of the rat small intestinal mucosa was considerably greater than both testis and lung, suggesting that the small intestine may make significant contribution to the peripheral oxidative metabolism of testosterone. In addition, the high specific activity of 17β-HSD in the small intestinal mucosa may be an important factor leading to testosterone's lack of oral potency.
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