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Perfusion of tissue with a medium containing two metabolically related compounds, each labeled with a different isotope, and measurement of isotopic concentrations at the steady state were used to calculate the rates at which the perfused tracers enter and leave the tissue. This novel experimental design was applied to the study of the dynamics of uptake of estrogens and androgens by human endometrium. Endometrial curettings were sliced and perfused with a buffer solution containing a mixture of 3H-17β-estradiol, 14C-estrone, 3H-testosterone and 14C-4-androstene-3,17-dione. An isotopic steady state was achieved while the tissue maintained its viability. Extensive interconversion between estrone and estradiol, and between testosterone and androstenedione, was observed. The fraction of a perfused tracer that entered the tissue slices was not affected by its concentration in the range tested and was practically equal for estrone, estradiol, testosterone, and androstenedione, when perfused as a mixture. It was, however, reduced when plasma was used instead of buffer solution. More than one-half of estrone (or androstenedione) entering the tissue was released back into the medium. Only a small fraction of estradiol (or testosterone) that entered the slices was discharged into the medium; it left the tissue mainly as estrone (or androstenedione). It was estimated that the fraction of the tracer present in the tissue in a diffusible form was about 20% for androstenedione, 5% for estrone, and less than 1% for estradiol and testosterone.
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Gurpide et al. (1969) studied this question.
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