Subcellular distribution of estradiol and estrone in human endometrium and myometrium during the menstrual cycle

Abstract The endogenous concentration and the subcellular distribution of estradiol-17β (E2) and estrone (E1) was measured in human endometrial and myometrial tissue during the menstrual cycle. An improved tissue fractionation and extraction procedure was used to measure quantitatively and specifically E2 and E1. The E2 concentraton in total tissue showed a large fluctuation over the cycle: E2 varies between 550 and 3460 pg/g in endometrium and between 380 and 1710 pg/g in myometrium. The concentration of E2 was higher in endometrium than in myometrium except for the secretory phase of the cycle. The E1 concentration was much lower than the E2 concentration with only small differences between endometrium and myometrium. The highest values for E1 and E2 were found in uteri taken at the mid-proliferative phase. The subcellular distribution of E2 and E1 was studied by measuring the concentration of both estrogens in the free cytosol fraction (CF), in the cytosol receptor-bound fraction (CR) and in the nuclear fraction (N). We found a progressive increase in the E2 concentrations from CF to CR and from CR to N. The largest increase was seen at the mid-proliferative phase. The tissue/plasma gradient reached in this phase was 1/1 for CF, 8/1 for CR and 25/1 for N. There was a sharp drop in nuclear E2 from the proliferative phase to the peri-ovulatory phase in both endometrium and myometrium. This decline in E2 concentration was not associated with an increase in E1. For E1 there was only a small tissue/plasma gradient with small differences between endometrium and myometrium and with minor fluctuations over the cycle. We conclude that E2 is the most abundant estrogen both in endometrium and myometrium, supporting the concept of E2 being the physiologically active hormone in these tissues. The sharp decline in E2 concentrations without an increase in E1, from the proliferative phase to the peri-o-vulatory phase, suggests that the anti-estrogenic effect of progestins can not be explained by only the induction of 17β-hydroxysteroid dehydrogenase alone.