Androgen Receptors Are Similar in Fetal and Adult Rabbits*

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Abstract
To explain the separate roles of testosterone and dihydrotestosterone (17.beta.-hydroxy-5.alpha.-androstan-3-one) in virilizing the male fetus, the binding of these androgens to cytosolic receptors from urogenital tract tissues of fetal and adult male rabbits was compared. As measured by a direct binding assay, fetal and adult androgen receptors are similar in respect to specificity, affinity, and amount of binding. Apparent Kd for dihydrotestosterone binding averaged 1.1 nM for fetal receptor and 0.8 nM for adult androgen receptors. Average apparent dissociation constants for testosterone binding were 4- to 24-fold higher than those for dihydrotestosterone in fetal and adult tissues. Nonradioactive dihydrotestosterone and testosterone competed for [3H]dihydrotestosterone binding to the androgen receptor in both adult prostate and fetal urogenital sinus in a manner consistent with their affinity for binding, whereas estradiol, progesterone, and cortisol were weak competitors for [3H]dihydrotestosterone. On sucrose density gradients, both testosterone and dihydrotestosterone were bound to a protein with a sedimentation coefficient of .apprx. 8S. Although androgen receptors were detectable in urogenital tubercle and urogenital sinus of both male and female fetuses on days 18 and 29 of gestation, androgen binding in fetal Wolffian ducts could not be characterized. The nature of the androgen receptor in this tissue remains unresolved. Dihydrotestosterone formation may act to amplify the androgenic signal in both the fetus and adult, but is not absolutely required for virilization.