Androgen Receptor Content of the Normal and Hyperplastic Canine Prostate

Abstract

A B S -R A C T A procedure was developed for rneeasurement of androgeni receptors in cytoplasmic extracts of prostates froms intact dogs. The protocol utilized exchange saturatioin analysis at 15°C employing the synthetic androgen R1881 (17,8-hydroxy-17an-methylestra-4,9, 1 1-trien-3-one) as the ligand probe anid quantitatively dletected total cytoplasmic androgeni receptor (R, anidrogen-free receptor, and R,.A, androgenoccupied receptor) present at the initiation of the assay. This protocol was employed in conjunctioni with a tissue mince saturation anialysis procedure (for (uantitation of nuclear androgen receptor) to (quanititate total androgeni receptor content of normal and hyperplastic prostates obtained fromi young (2.5-or 4.6-yr old) and aged (12.5-yr old) purebred dogs of known birth date.The total cytoplasmic androgeni receptor content (piconmoles per prostate) of hyperplastic prostates was 4.6-fold greater than that of normal prostates. The total nuclear androgen receptor content of hyperplastic prostates (piconmoles per prostate meassured in crude nuclear preparations) was either 5.0-(4.6-yr-old dogs) or 7.8-fold (2.5-yr-old dogs) greater than that of normnal prostates. However, androgen receptor content per cell was identical for hyperplastic and normal canine prostates, with the exception that nuclear androgeni receptor was diminished in prostates fromii 2.5-yr-old dogs. The the molecular mlechanismiis of hornmone action have led to an increasing number of investigations of hormonal regulationi of caniine prostate functioni (4-10). Although histologic features (11) and hormone sensitivity (3,4,(12)(13)(14) of the two prostatic hyperplasias differ, the induction of canine prostatic hyperplasia by injection of anidrostaniediol' or anidrostanediol plus 17,8-estradiol (9) suipports the use of the caniine model for studies of pathogenesis. When compared to normal prostates, 1)oth humilan anid caninle prostatic hyperplasia are characterized by an approximately fivefold increase (7,15) in the conicentrationi of the prostatic androgen 5a-dihydrotestosterone (16). However, the rate of conversion of testosterone to 5a-dihydrotestosterone is not significantly different for normal and hyperplastic prostates of either specie (7, 15). The observations suiggest that an alteration in the mechanism of 5a-dlihydrotestosterone accumulation may be related to the pathogen esis of prostatic hyperplasia.Current concepts of the mechanism of steroid hormone regulationi of cell function envisions a process whereby effector steroid initially interacts with cytoplasmic receptor proteins. The highly steroid specific b)inding of effector to cytoplasmic receptor protein promotes translocationi of the receptor-steroid complex into the nuclear compartment (17,18). Consequently, the capacity of the prostate to specifically accumulate 5a-dihydrotestosterone (effector steroid) would be expected to be related to the tissue cointenit of cytoplasmic and nuclear androgen receptor. As part of a study of aging-associated changes in st...

The impact of finasteride and dutasteride treatments on proliferation, apoptosis, androgen receptor, 5α-reductase 1 and 5α-reductase 2 in TRAMP mouse prostates

“…This may demonstrate the absence of finasteride or dutasteride treatment-associated effect in TRAMP mice large tumor AR expression. There was a notable increase in AR levels in hyperplasia versus prostate epithelium, which is similar to the high total cytoplasmic and nuclear AR content of hyperplastic prostates versus normal prostates in 2.5- to 4.6-year-old dogs [50] . AR was mostly increased in prostate epithelium versus tumor in treatment groups, which is similar to the significant increase in AR levels in benign versus tumor in human prostate following finasteride treatment [49] .…”

The Effects of Aging on the Molecular and Cellular Composition of the Prostate Microenvironment

“…Autopsy studies indicate that prostate cancer incidence approaches 60–70% in the 8th and 9th decade of life [12] , [13] . A relationship between aging and inflammation, hyperplasia and neoplasia of prostatic tissue has also been observed in rodents and dogs [14] , [15] , [16] , [17] . Overall, the etiology of these diseases remains poorly defined despite causing substantial morbidity and mortality in the population.…”

Relations between Circulating Levels of Testosterone, 17β-Estradiol, Androstenedione, Dehydroepiandrosterone Sulfate, and Androgenic Receptor Content of Cytosol in Benign Prostatic Hyperplasia

“…In creased androgenic receptors have been shown in benign prostatic hyperplasia (BPH), relative to normal prostate, in dogs [3,4] as well as in man [5,6], Experimental induc tion of hyperplasia via estrogens [2] or via synergistic action of estrogens and androgens [3] produce an eleva tion in androgenic receptor content, accompanied by an increase in prostatic growth [2,3]. These results have led to suggestions that increases in androgenic receptors re present a mechanism in the development of prostatic hyperplasia [1][2][3].…”