Antiestrogen Modulation of the Salt-Resistant Nuclear Estrogen Receptor*

Abstract

Studies were performed in vivo to determine the ability of the antiestrogen U-11.100A (UA) to modulate the binding of the estrogen receptor to uterine nuclei. UA (100 μg) injected at 30, 60, or 120 min into immature female rats arrested the rapid estradiol receptor complex (ERC) clearance from the nuclei after the 1-h accumulation which normally occurs after a single 5-μg injection of 17β-estradiol (E2). The UA receptor complex was then accumulated in the nuclei and retained for at least 48 h. As there is no indication that there is any significant replenishment of the cytoplasmic estrogen receptor within the first 12 h after a UA (100 μg) injection or after an E2 (5 μg) injection followed by a subsequent UA (100μg) injection at 30, 60, or 120 min, the UA appears to be recapturing estrogen receptors initially translocated to the nuclei. However, by 24 h after a UA injection, there is replenishment of the cytoplasmic estrogen receptor, and subsequent E2 injections at this time will cause the nuclear translocation of ERC and the maximal formation of the KCl-resistant ERC (about 0.22 pmol/uterus). After a single injection of E2 (5 μg), there is a period of a few hours in which a subsequent injection of E2 is unable to induce the nuclear accumulation of ERC. Only when there is sufficient replenishment of cytoplasmic estrogen receptor can a reaccumulation of the nuclear ERC occur with subsequent E2 injections. The formation of the KCl-resistant form of the ERC by a single injection of E2 (5 μg) appears by 15 min, and is maximal at 30 min, remaining at this level for approximately 2 h with a gradual decrease by 6 h. This pattern could also be modified by antiestrogens. UA (100 μg) injected 30 or 60 min after E2 (5 μg) resulted in the immediate loss of the KClresistant ERC. This would seem to indicate that the antiestrogen was capable of exchanging with E2 on the salt-resistant nuclear estrogen receptor, causing conversion of the estrogen receptor from a KCl-resistant form to a KCl-extractable form. (Endocrinology102: 1838, 1978)