Tissue differences in estrogen receptor dynamics: Nuclear retention, rate of replenishment, and transient receptor loss vary in hypothalamus, pituitary, and uterus of c57bl/6j mice

Little is known about tissue differences in estrogen receptor (ER) dynamics, despite evidence that they could play a role in the tissue specificity of estrogen action. This study was designed to test the hypothesis that ER dynamics differ in uterus (UT), pituitary (PIT), and hypothalamus (HYPO), as measured by 1) duration of peak nuclear ER (ERn), 2) rate of replenishment of cytosolic ER (ERc), and 3) loss of total ER (ERt) after a bolus of estradiol (E2). Young adult mice were studied at two hormonally distinct stages of the cycle [days 2 or 3 (D2–3) and D5 (Dl = proestrus)]. Animals were injected with a dose of E2 (0.05 µg/10 g BW) sufficient to achieve maximal ERn or with vehicle only, and ER was determined in nuclear and cytosolic fractions 1, 2, 4, 8, 12, and 24 h later. ERn peaked concomitantly with plasma E2 at 1 h in all tissues, but the duration of peak ERn varied among tissues: 4 h in HYPO compared to 1–2 h in UT and PIT. ERc replenishment was complete by 12 h in HYPO, but not until 24 h or more in PIT; replenishment in UT was intermediate (12–24 h). The transient loss of ERt after E2 injection was pronounced in UT and PIT, but was undetectable in HYPO. These tissue differences were maintained across cycle state, despite effects of cycle state on ER dynamics. The effects of cycle state on ER dynamics were also tissue specific; they were greatest in UT and absent in HYPO. On D2–3 in UT, ERn and ERt were lower, and replenishment of ERc was slower than on D5. Parallel effects of cycle state were seen in PIT, with the exception of ERn, which was unaffected. Because altered ER dynamics similar to those observed on D2–3 can be produced by progesterone pretreatment, the altered ER dynamics on D2–3 may be a consequence of recent exposure on Dl to the ovulatory surge of progesterone. Taken together, these results indicate that the mechanisms governing intracellular ER dynamics vary markedly among tissues and provide an impetus for further examination of their role in the tissue specificity of estrogen action.