Specific Androgen Binding in the Kidney and Estrogen-Dependent Renal Carcinoma of the Syrian Hamster1

The presence of a specific dihydrotestosterone (5α-DHT) 9 S receptor complex has been detected in the renal cytosol of untreated castrate male hamsters using sucrose gradient analyses. The amount of this receptor is enhanced more than 3-fold by 5α-DHT treatment. Although prolonged estrogen treatment augments the amount of specific progesterone binding in the hamster kidney, the quantity of specific androgen receptor remained at normal levels. The amount of specific androgen binding found in the estrogen-induced renal tumor cytosol of the hamster was at least 64 times and 17 times normal and 5α-DHT-treated levels, respectively, and sediments as an 8 S component in low salt sucrose gradients. The renal carcinoma 5α-DHT receptor sedimented at 6 S and 4 S when 0.15M and 0.4M KC1 was present in the gradient, respectively. Competition studies indicate that these androgen receptors are specific since aldosterone and glucocorticoids do not compete for these receptors at 100-fold excess whereas inhibition is nearly complete at 50- and 100-fold unlabeled 5α-DHT. Cyproterone acetate caused marked inhibition of the [3H]5α-DHT cytosol receptor binding in vitro but flutamide was considerably less effective as an inhibitor under the same conditions at comparable concentrations. Interestingly, significant inhibition of the 5α-DHT binding was observed when nonlabeled estradiol (50 × and 100 ×) or progesterone (100 ×) was used, whereas only negligible competition was observed with corresponding concentrations of diethylstilbestrol, estrone, and estriol. Competition studies indicate that the androgen receptors in the seminal vesicle, kidney, and renal carcinoma are similar. Scatchard plot reveals the cytosol- 5α-DHT receptor complex of the 5α-DHT-treated kidney and the renal tumor has a Ka of 0.74–0.78 × 109M−1 and 0.6–1.1 × 109M−1, and has 0.10 × 10−10M and 2.72 × 10−10M binding sites per mg protein, respectively. Translocation of the renal androgen receptors from both 5α-DHT-treated hamsters and renal tumor resulted in a 3.2 S nuclear binding moiety under in vitro conditions.