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13 Increased androgen binding capacity in experimental prostatic carcinomas treated with estrogen
5s
13
INCREASED
ANDROGEN
BINDING
CAPACITY
B.G. Mobbs and I.E. Johnson, Toronto, Canada MSS lA8
IN EXPERIMENTAL PROSTATIC CARCINOMAS ESTROGEN Dept. of Surgery, University of Toronto
TREATED
WITH
We have previously reported very high concentrations of high affinity androgen binding sites in cytosol from prostatic carcinomas of some patients who had been treated with estrogen. We have now demonstrated a similar phenomenon in the R3327H (Dunning) prostatic carcinoma model. Tumour-bearing rats were either (i)left untreated, (ii)castrated, or (iii)treated with diethylstilbestrol (DES). Tumours were excised after 2d-20wks. treatment. Free and total cytosol and nuclear androgen binding was investigated using 3H-methyltrienolone (3H-R1881) as ligand under conditions which conserve androgen receptor and prevent binding to normal progesterone receptor. Considerable tumour variation was observed within each treatment group, but some statistically significant differences were found in androgen binding capacity, in cellular distribution and in occupancy of cytosol binding sites as determined by the exchange assay. Castration decreased the concentration and proportion of cytosol sites assayable only under exchange conditions, but long term DES treatment increased the concentration of both free and occupied cytosol sites. Both treatments reduced nuclear binding to insignificant levels. Scatchard analysis, sucrose density gradient centrifugation and steroid competition studies were used to characterize 3H-R1881 binding in some tumours.
F. Schroeder Abstract
15
not received
EFFECT OF MEDICAL OR SURGICAL CASTRATION ON PROSTATIC STEROID CONTENT IN THE DOG A. BELANGER, Y. TREMBLAY, F. LABRIE, R.R. TREMBLAY AND J. DUBE Depts of Molecular Endocrinology and Endocrinology-Metabolism, CHUL, Quebec GlV 4G2, Canada Administration for three months of the potent LHRH agonist [D-Serethylamide (25 ug) to adult dogs having (TBU) 6, des-Gly-NH21°]LHRH spontaneous benign prostatic hyperplasia (BPH) causes a rapid and almost complete inhibition of serum dihydrotestosterone (from 225 f 55 + 220 to 325 i 30 pg/ml) to 30 * 30 pg/ml) and testosterone (from 1235 This inhibition of A4-androgen secretion is accompanied concentration. and So-androgen metaby a decrease of testicular progestin precursors Measurement of prostatic steroid content shows that adminisbolites. tration of the LHRH agonist as well as castration are associated with a marked decrease in androstenedione (from 0.85 * 15 to 0.07 * 2 ng/g), 2 0.02 rig/g)) and dihydrotestostestosterone (from 0.42 + 0.12 to 0.051 ? 0.05 rig/g)) levels while there is terone (from 6.02 + 0.12 to 0.31 only a small inhibition of androst-5-ene-33,17il-diol, androstaneand estrone concentrations in the dehydroepiandrosterone 3B,17B-dial, surgical as well as medical prostate. The present data show that after relatively high levels of castration the prostate can still contain steroids which could well exert important local effects.
13
INCREASED
ANDROGEN
BINDING
CAPACITY
B.G. Mobbs and I.E. Johnson, Toronto, Canada MSS lA8
IN EXPERIMENTAL PROSTATIC CARCINOMAS ESTROGEN Dept. of Surgery, University of Toronto
TREATED
WITH
We have previously reported very high concentrations of high affinity androgen binding sites in cytosol from prostatic carcinomas of some patients who had been treated with estrogen. We have now demonstrated a similar phenomenon in the R3327H (Dunning) prostatic carcinoma model. Tumour-bearing rats were either (i)left untreated, (ii)castrated, or (iii)treated with diethylstilbestrol (DES). Tumours were excised after 2d-20wks. treatment. Free and total cytosol and nuclear androgen binding was investigated using 3H-methyltrienolone (3H-R1881) as ligand under conditions which conserve androgen receptor and prevent binding to normal progesterone receptor. Considerable tumour variation was observed within each treatment group, but some statistically significant differences were found in androgen binding capacity, in cellular distribution and in occupancy of cytosol binding sites as determined by the exchange assay. Castration decreased the concentration and proportion of cytosol sites assayable only under exchange conditions, but long term DES treatment increased the concentration of both free and occupied cytosol sites. Both treatments reduced nuclear binding to insignificant levels. Scatchard analysis, sucrose density gradient centrifugation and steroid competition studies were used to characterize 3H-R1881 binding in some tumours.
F. Schroeder Abstract
15
not received
EFFECT OF MEDICAL OR SURGICAL CASTRATION ON PROSTATIC STEROID CONTENT IN THE DOG A. BELANGER, Y. TREMBLAY, F. LABRIE, R.R. TREMBLAY AND J. DUBE Depts of Molecular Endocrinology and Endocrinology-Metabolism, CHUL, Quebec GlV 4G2, Canada Administration for three months of the potent LHRH agonist [D-Serethylamide (25 ug) to adult dogs having (TBU) 6, des-Gly-NH21°]LHRH spontaneous benign prostatic hyperplasia (BPH) causes a rapid and almost complete inhibition of serum dihydrotestosterone (from 225 f 55 + 220 to 325 i 30 pg/ml) to 30 * 30 pg/ml) and testosterone (from 1235 This inhibition of A4-androgen secretion is accompanied concentration. and So-androgen metaby a decrease of testicular progestin precursors Measurement of prostatic steroid content shows that adminisbolites. tration of the LHRH agonist as well as castration are associated with a marked decrease in androstenedione (from 0.85 * 15 to 0.07 * 2 ng/g), 2 0.02 rig/g)) and dihydrotestostestosterone (from 0.42 + 0.12 to 0.051 ? 0.05 rig/g)) levels while there is terone (from 6.02 + 0.12 to 0.31 only a small inhibition of androst-5-ene-33,17il-diol, androstaneand estrone concentrations in the dehydroepiandrosterone 3B,17B-dial, surgical as well as medical prostate. The present data show that after relatively high levels of castration the prostate can still contain steroids which could well exert important local effects.