The daily plasma productionrate of testosterone was measured in normal men and women and in 2 patients with the complete form of the syndrome of feminizing testes from the product of the metabolic clearance rate of testosterone in plasma as determined following a single injection of the tritiated hormone, and the mean plasma nonisotopic concentration of the steroid. The latter values were obtained from the mean of plasma testosterone levels obtained at 9 am, 5 pm and 10 pm. A significant diurnal variation was found in the normal men but not in the normal women. The mean plasma concentration of testosterone in these subjects was 0.52 and 0.06 μg/100 ml, respectively. The metabolic clearance rates in the normal men (1670–2084 I/day) were approximately twice those obtained in normal female subjects (708–759 I/day). The difference appeared to be due primarily to a larger inner pool volume (V,) (Vs where K2 = 0) in the males. The plasma production rates of testosterone were 10.8, 6.8, 10.0 and 6.7 mg/day in males and 0.49, 0.49 and 0.44 mg/day in normal females. The male values compared reasonably well with those reported for the urinary testosterone glucuronoside method. However, in the female the daily plasma production rates of testosterone were considerably less than those obtained by the urinary metabolite technique. This suggests that in women, in contrast to men, a significantly greater proportion of total testosterone is synthesized from precursors in a separate anatomical compartment and conjugated before entering the circulation. Thus, the error involved in the measurement of testosterone production by the urinary metabolite method is considerably greater in women than in men. In the subjects with the syndrome of feminizing testes the inner pool volume (Vi) and the total volume of distribution (V1+V2) were similar to those observed in the normal adult females. The metabolic clearance rates of testosterone were 954 and 1072 I/day and this gave calculated plasma production rates of the steroid of 6.5 and 9.6 μg/day. The presence of normal adult male production rates of testosterone provides additional evidence in favor of the view that the manifestations of the syndrome are related to a defect in androgen action.

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