Comparison of spontaneous and experimentally induced canine prostatic hyperplasia.

Abstract

A B S T R A C T Spontaneous prostatic hyperplasia in the beagle appears to progress with age from a glandular to a cystic histological appearance. Prostatic hyperplasia can be induced in young beagles with intact testes by treatment for 4 mo with either dihydrotestosterone or 5a-androstane-3a,17,8-diol, alone, or with either of these steroids in combination with 17,3-estradiol.In contrast, the induction of prostatic hyperplasia in young castrated beagles, in which the gland had been allowed to involute for 1 mo, requires the administration of both 17,3-estradiol and either 5a-androstane-3a, 17,8-diol or dihydrotestosterone. Testosterone and 17,8-estradiol, either singly or in combination, did not produce the hyperplastic condition in intact or castrated beagles. The experimentally induced prostatic hyperplasia is identical in pathology to the glandular hyperplasia that occurs naturally in the aging dog with intact testes. However, cystic hyperplasia was not produced by any of the treatments tested in young animals.

Models for studying benign prostatic hyperplasia

“…61 In contrast to that in man, the enlarged prostate in the dog rarely results in urethral obstruction. 62 Broderick et al 63 developed a canine model of BPH that will secondarily result in partial urethral obstruction and impaired urodynamics.…”

“…19 In these animals, BPH is also an age-related disease. The onset of BPH in the dog may occur at as early as 2 ± 3 y of age, 61 but it occurs with high frequency in aged dogs. 64,65 Microscopic BPH was observed in all dogs after 6 y of age.…”

“…66 The disease is often a multinodular process thought to arise as periurethral stromal nodules which are then invaded by glandular elements. 61 In man, PSA is produced only by epithelial cells and is found in normal, hyperplastic and malignant prostatic tissue. Serum PSA concentrations have been used to evaluate prostate volume in man.…”

“…Canine BPH is uniform and diffuse, occurring thoughout the entire gland and it primarily involves the glandular epithelial cells, with less stromal involvement. 45,61,65,67,68 Tunn and his colleagues 69 reported that the concentration of 5a-reductase, which converts testosterone to dihydrotestosterone, an active androgen, is higher in the prostatic epithelium than in the stroma in dogs. This is not the case in man which may explain why the hyperplasia is mainly epithelial in dogs and stromal in men.…”

Identification of the molecular switch that regulates access of 5α-DHT to the androgen receptor

“…3α-Diol is a weak androgen K d of 10 −6 M for the AR that is incapable of transactivation. Studies in rats (Orlowski, et al, 1983), dogs (DeKlerk, et al, 1979;Jacobi, ,et al 1978), marsupials (Shaw, et al, 2000) and humans (Horst, et al, 1975) have demonstrated that 3α-diol can be converted back to 5α-DHT to stimulate growth of the prostate, but the identity of the oxidative 3α-HSD responsible for this back reaction has remained elusive. Our data shows that "RoDH like 3α-HSD" (a short-chain dehydrogenase /reductase (SDR)) (Biswas and Russell, 1997) is responsible for this reaction in human prostate.…”