Induction of benign prostatic hyperplasia in intact dogs by near‐physiological levels of 5α‐dihydrotestosterone and 17β‐estradiol

Abstract

Benign prostatic hyperplasia was induced in mongrel dogs treated for 60 days with one silastic implant containing 17 beta-estradiol and four containing 5 alpha-dihydrotestosterone. The condition was characterized by (1) a marked increase of the stromal elements, particularly the stromal septa between the individual glands, (2) a slight increase in prostatic volume, and (3) a morphology that resembled spontaneous complex benign prostatic hyperplasia in the dog. Other groups of animals that remained untreated or received only 17 beta-estradiol or only 5 alpha-dihydrotestosterone did not develop this condition. Prostate volumes decreased by 14% in the estrogen-treated dogs, whereas they increased in the androgen-treated animals by 6% compared to pretreatment prostate volumes. The morphology of the epithelium of the prostates of androgen-treated animals was not different from that of controls despite the increase in prostate volume. The serum 17 beta-estradiol and 5 alpha-dihydrotestosterone concentrations were increased from 25 +/- 2 (mean +/- SEM) and 256 +/- 42 pg/mL, respectively, in control dogs to 52 +/- 37 and 562 +/- 37 pg/mL, respectively, in the dogs treated with the hormone combination. Thus, hormone concentrations were two- to three-fold higher than control values, and the ratio of estradiol-17 beta to 5 alpha-dihydrotestosterone was increased by up to 19%. These data demonstrate that treatment of dogs with low levels of estrogen and androgen may be an excellent model for the study of spontaneous complex benign prostatic hyperplasia in aging men.

Anabolic effects of testosterone are preserved during inhibition of 5α-reductase

“…Another intriguing possibility relates to the duration of testosterone treatment. Although DHT is considered the chief mediator of prostate enlargement, Winter et al (47) have shown that prostate enlargement in dogs is caused by administration of DHT plus a small dose of 17␤-estradiol, but not by DHT alone, indicating that a small amount of estrogen is required for prostate enlargement. Because administration of androgens inhibits endogenous testosterone secretion and because estrogen can be synthesized from testosterone, but not DHT, it is expected that prostate estrogen concentration would be increased by testosterone administration and decreased by DHT administration (45).…”

Life expectancy, antagonistic pleiotropy, and the testis of dogs and men

“…Curiously, BPH and prostatic cancers develop spontaneously in the prostates of aging dogs and men at a life stage when testicular androgen production is declining, suggesting that nonandrogen factors may also be important [5,6]. Experimental manipulations in dogs suggest that androgens and estrogens might act synergistically to induce BPH [7].…”

Stromal and epithelial cells of the canine prostate express parathyroid hormone-related protein, but not the PTH/PTHrP receptor

“…The dog is widely used for prostate research due to the high incidence of benign prostatic hyperplasia in this species [17,18]. Although biologic dissimilarities exist between the human and the canine prostates, dogs have proved to be a valuable tool for the study of prostate biology and pathology and for the testing of pharmaceuticals [19][20][21][22].…”