REGULATION OF CYTOSOL AND NUCLEAR PROGESTERONE RECEPTORS IN RABBIT UTERUS BY ESTROGEN, ANTI-ESTROGEN AND PROGESTERONE ADMINISTRATION

A synthetic progestin, 16α-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione (ORG 2058), was utilized to measure progesterone receptors from the rabbit uterus. This steroid has a high affinity for both cytosol and nuclear receptors, with KD values of 1.2 nM (at 0-4°C) and 2.3 nM (at 15°C), respectively. Administration of estradiol-17β or a non-steroidal antiestrogen, tamoxifen, for 5 days to estrous rabbits led to a progressive rise in the cytosol receptor levels: from 34 000 to 120 000 (estradiol-17β) and 80 000 (tamoxifen) receptors/ cell, without any major influence on the nuclear receptor content. A single intravenous injection of progesterone (5 mg/kg) elicited a 3-fold increase in the mean nuclear receptor content at 30 min after injection (from 18 000 to 48 000 receptors/nucleus). Nuclear receptor accumulation was short-lived and returned to control levels within 4 h after treatment. A second dose of progesterone given 24 h later doubled the nuclear receptor level (from 18 000 to 35 000 receptor/nucleus). The concomitant decline in the cytosol receptor content was twice that accounted for by the nuclear receptor accumulation (70 000 vs. 30 000, and 40 000 vs. 17 000 receptors/cell, after the first and second progesterone injection, respectively). Following progesterone administration, the cytosol receptor level reached a nadir by 30 min, exhibited minimal replenishment within the ensuing 24 h, and remained at approx. 50% of the pretreatment values. After a single dose or two consecutive doses of progesterone, total uterine progesterone receptor content declined to about 60% of the level prior to each dose, a nadir being reached at 2 h after treatment. © 1979.