Effects of ageing and hormonal manipulations on the level of oestrogen receptors in the guinea-pig prostate.

Abstract

Cytosolic oestrogen receptor levels in guinea-pig prostate tissue were found to decrease with increasing age, irrespective of whether the binding was expressed relative to cytosolic protein or cellular DNA. This decrease in oestrogen receptor levels was also observed using enriched fibromuscular stromal tissue prepared by mechanical fractionation of the prostate. The most pronounced change in cytosolic oestrogen receptor levels (from 133 to 35 fmol/mg protein) occurred at the onset of puberty. The pubertal decrease in receptor levels could not be attributed to an increase in the level of proteolytic activity in prostatic cytosol fractions derived from mature animals, a change in the affinity of the receptor for oestradiol or an increase in oestrogen receptor levels in salt-extracted nuclear fractions. Administration of tamoxifen (1 mg/day) to intact guinea-pigs throughout the transpubertal growth phase did not influence the age-related decrease in cytosolic and nuclear oestrogen receptor levels. In contrast, the decrease in oestrogen receptor levels was prevented by castration. Administration of dihydrotestosterone (DHT; 1 mg/day) to intact prepubertal animals for 4 days before study resulted in diminished cytosolic oestrogen receptor levels; this effect of DHT was blocked by the non-steroidal antiandrogen flutamide (2 mg/day). Furthermore, elimination of testicular hormones by castration during the late-pubertal growth phase resulted in a greater than twofold increase in prostatic oestrogen receptor levels. Collectively, these observations suggest an age-related decrease in oestrogen receptor levels in the guinea-pig prostate which, in part, may be due to increased testicular function at puberty.