In VivoUptake and Subcellular Distribution of Tritium- Labeled Estrogens in Human Endometrium, Myometrium, and Vagina

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Abstract
Uptake, retention, and subcellular distribution of 17β-estradiol (E2), estrone (E1), and estriol (E3) in endometrial, myometrial, and vaginal tissue in 18 normal postmenopausal women under physiological conditions were studied by giving [3H]E2, [3H]Ei, or [3H]E3 in subphysiological doses by continuous infusion lasting 12 h before hysterectomy. Endometrial, myometrial, and vaginal tissues from each woman were separated into five cellular fractions: two cytosol fractions (free estrogen fraction and specifically bound fraction) and three nuclear fractions. The results show an accumulation of [3H]E2 in the target tissue after [3H]E2 and [3H]Ei infusions; we found an approximately 30 times higher [3H]E2 concentration after [3H]E2 infusion in endometrium (disintegrations per min/ g) than in plasma (disintegrations per min/ml), 20 times higher in myometrium, and 10 times higher in vaginal tissue. The corresponding [3H]Ei tissue to plasma ratios were 7, 4, and 6, respectively, for endometrium, myometrium, and vagina. [3H]Ei infusion did not result in steady state conditions in estrogen metabolism in the tissues. Arguments are presented to substantiate that the accumulation of E2 in the tissues is derived from the uptake of plasma E2 originating from plasma Ei. After continuous administration of [3H]E3, the tissue to plasma gradient of [3H]E3 was 37 in endometrial, 19 in myometrial, and 11 in vaginal tissue. A metabolite of [3H]E3 observed in plasma and tissue could tentatively be identified as 16ahydroxyestrone. The subcellular distribution shows that 60-80% of E2 and E3 is accumulated in the nuclear cell fractions of all tissues studied, while a relatively small accumulation of Ei is found in the CF fraction. No nuclear bound Ei could be detected. We conclude that 1) E2 is the major tissue estrogen and is mainly nuclear bound in endometrium, myometrium, and vagina of postmenopausal women; 2) plasma E] is a prehormone for the biologically active plasma E2; the intracellular Ei concentration results largely from the conversion of E2; 3) the endometrium of postmenopausal women accumulates more E2 and E3 than vaginal tissue from the same individual (per g tissue); and 4) no preferential accumulation of E3 in vaginal tissue is found under physiological circumstances.