Castration levels of plasma testosterone have potent stimulatory effects on androgen-sensitive parameters in the rat prostate.
In order to assess the biological significance of low serum androgens comparable to those which remain after castration in men treated for prostate cancer. Silastic depots continuously releasing predetermined doses of testosterone (T) have been implanted into castrated adult male rats in the absence or presence of simultaneous treatment with the pure antiandrogen Flutamide. Quite remarkably, a 3- to 5-fold increase in prostate weight (P less than or equal to 0.001) was observed at plasma T concentrations comparable to those found in the serum of castrated men. Although of lower magnitude, castration levels of plasma T also caused a significant stimulation of seminal vesicle weight (P less than 0.01). This dramatic stimulatory influence of "castration" levels of plasma T on ventral prostate and seminal vesicle weight can be explained by the 13- to 15-fold higher intraprostatic level of the active androgen dihydrotestosterone (DHT) compared to the plasma T concentration. In fact, a near-maximal intraprostatic concentration of DHT is reached at concentrations of plasma T of 0.2-0.5 ng/ml and a positive correlation was found between prostatic DHT concentration and ventral prostate weight. Prostatic growth and DHT concentrations were also positively correlated with ornithine decarboxylase (ODC) activity, an enzyme highly sensitive to androgens in the rat ventral prostate. In fact, a dramatic (30-fold) increase in ODC activity was observed at plasma T values corresponding to those found in castrated men. The level of prostatic beta 2-adrenergic receptors fell within 10 days of castration and an increase in beta 2-adrenergic receptor concentration was observed with low doses of T, thus indicating that beta 2-adrenoreceptor levels are also a sensitive parameter of androgenic activity in the rat prostate.(ABSTRACT TRUNCATED AT 250 WORDS)
Marchetti
B
B
MRC Group in Molecular Endocrinology, Le Centre Hospitalier de l'Université Laval, Quebec, Canada.
Poulin
R
R
Plante
M
M
Labrie
F
F
D000818:Animals; D013196:Dihydrotestosterone / Q000378:metabolism; D005485:Flutamide / Q000494:pharmacology; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011467:Prostate / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012669:Seminal Vesicles / Q000033:anatomy & histology; D013739:Testosterone / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D013196:Dihydrotestosterone; D013739:Testosterone; D005485:Flutamide; D009955:Ornithine Decarboxylase