Androgen Dynamics in Vitro in the Canine Prostate Gland

Abstract

The uptake and metabolism of androgens by canine prostate in vitro were studied by means of an experimental design which consisted of superfusion of prostate slices with a medium containing [4-14C]androstenedione and [6,7-3H]testosterone, or [4-14C]testosterone and 5\g=a\-dihydro[1,2-3H]testosterone. The entry or transfer of steroids into the slices, the irreversible metabolism, the conversion between the steroids and their uptake or tissue retention were measured at the steady state. A similar proportion of the three androgens entered the tissue and was irreversibly metabolized. Conversion of testosterone into 5\g=a\-dihydrotestosterone was much greater than the interconversion of testosterone and androstenedione. The prostate slices retained 5\g=a\-dihydrotestosterone in a concentration up to four times that in the medium, whereas testosterone and androstenedione were retained to a smaller extent.By increasing the steroid concentration in the perfusing medium from 0\m=.\03 to 1\m=.\30 \g=m\mol/l, it was shown that the systems regulating entry, uptake and metabolism of the androgens were not saturated within this range of concentration. No substantial differences were observed in the regulation of tissue\p=m-\androgen interaction in vitro between five normal and four hyperplastic canine prostates. This was in contrast with previously reported findings that, in man, normal and hyperplastic prostatic tissue respond in a different way to an increase in steroid concentration in the medium.

Studies on Androgen Transport Into Canine Prostate in Vitro

“…In all the experiments, the steroids had reached steady-state when the determinations used for the calculation of the parameters were made. Since it has been shown that there is no difference in androgen entry or efflux between normal and hyperplastic canine prostate (Giorgi, Stewart, Grant & Reid, 1972), the results obtained in these two types of tissue have been described together.…”

Effects of Estrogen on Growth of Androgen-responsive Rat Prostatic Tumor (R 3327).

“…The synergistic effects of estrogen on androgenic action may be explained, in part, by increased secretion of prolactin [6], but mostly it seems to be attributable to the direct action of estrogen on the target tissues of androgen [7]. It has been reported that estrogen causes increased permeability of cell membrane [8], interaction with androgen receptor [9], and an increase in DNA synthesis [10]. Together with these various effects, treatment with estrogen increases the weight of prostate and seminal vesicle in castrated testosterone-injected animals.…”

New Approaches for the Treatment of Prostatic Hypertrophy and Cancer

“…These 5-alpha-reduced metabolites act as the intra cellular mediators for many of the multiple actions of testosterone [1][2][3][4]. In the prostate, testosterone is also converted into delta-4-androstenedione (delta-4-A), 5-alpha-androstanedione (5-alpha-A) and androsterone (A) [2,[5][6][7][8][9][10][11][12], Benign prostatic hypertrophy (BPH), a common disease in aging men, is frequently associated with increased local 5-alpha-re ductase activity as well as with high tissue concentrations of DHT [13][14][15], The relc-vance of the intraprostatic accumulation of DHT as a possible factor in the development of the disease is underlined by the observa tion that BPH appears exclusively in hu mans and in dogs, i.e. in the only two species in which intraprostatic concentrations of DHT and of the 5-alpha-reductase increase with age [13,14,16].…”