Androgen Action And Metabolism Of T

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Androgen action appears to be mostly maintained with aging, but this has not been studied extensively. Androgen binding sites in the hippocampus, penile tissues, and genital skin are decreased in aging men and animals (Roehrborn et al., 1987; Tohgi et al., 1995). It is recognized that shortening of the CAG repeat in the androgen receptor increases androgen action, but it is not likely that this, per se, changes with aging (Lamb et al., 2001). It will be important to determine if there are age-related changes in coactivators and corepressors that are important in mediating androgen action at the cellular level.

T is metabolized to dihydrotestosterone (DHT) and to estradiol (E2) in tissues that have 5«-reductase activity and/or aromatase activity. DHT is a very potent androgen at the tissue level. It contributes most of the androgenic effects in genital tissues, accessory sex organs, and hair follicles. Five-alpha-reductase activity also is present in some areas of the brain and in bone (Russell et al., 1994). Aromatase activity is primarily present in adipose tissue, so most of the circulating estradiol and estrone in males comes from peripheral conversion of T and andro-stenedione (Simpson et al., 1997). T production rates in young adult males range between 4 and 10 mg/24 hours with an average of 6.6 mg/24 hours (Vermeulen, 1976). In men over age 65, the mean production rate decreases to approximately 4 mg/24 hours. Plasma levels of T reflect an age-related decrease in both secretion and the metabolic clearance rate.

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