Abstract
Using a modification of the collagenase dispersion method of Dufau et. al., we examined the estrogen receptor (RE) systems in both cytosol and nuclear preparations of Leydig cell concentrates from testes of a tumor susceptible (BALB/c) and a tumor resistant (C3H) strain of mouse. The testicular content of diethylstilbestrol (DES) and its metabolites was found to be similar in the two strains following the daily subcutaneous injection of [3H]-DES for 7 days suggesting a similar exposure of the Leydig cells to the hormone during periods of chronic administration. The characteristics of the cytosol RE in untreated animals of the two strains were similar with a dissociation constant (Kd) approximating 5 × 10−9 M. In untreated animals the level of RE in the cytosol per 107 Leydig cells was 201.7 ± 15.5 fmol (mean ± SE) in the BALB/c and 164.3 ± 12.0 fmol in the C3H (n = 4). A single injection of 2.5μg DES resulted in greater increase of nuclear receptor 0.75 h later in BALB/c than in C3H (95.3± 16.2 fmol vs 32.3 ± 4.4 fmol/107 Leydig cells, n = 3). The chronic administration of the estrogen to BALB/c caused a slight depletion of the cytosol RE at 3 days, followed by gradual increase so that after 3 months the level was more than twice that present originally. DES treatment also caused a similar pattern of the cytosol RE level in C3H animal, however, the magnitude of RE increment was somewhat less than in BALB/c animal. The response of the nuclear RE was rather different jn the two strains. After 1–2 weeks of treatment, the nuclear RE of C3H Leydig cells was essentially that noted 0.75 h after a single injection of DES, and it remained at this rather low level throughout the period of the study. In the BALB/c animals, on the other hand, after an initial sharp increase the nuclear receptor content rose gradually to levels 150% above those seen 0.75 h after a single injection of DES. The percentage of labelled estrogen extracted from nuclei with 0.4 M KCl was consistently smaller from BALB/c (74–80%) than from C3H (90–93%) so that after three months of DES treatment the nuclei of BALB/c mice had more than 10 times as much unextractable estrogen per nucleus as did C3H animals. Such differences in the RE system within the target cell could certainly contribute significantly to the great difference noted in the induction of Leydig cell hyperplasia and neoplasia by chronic estrogen administration to these two strains of mice.
Published Version
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