Characteristics of flutamide action on prostatic and testicular functions in the rat.
The effect of daily treatment with the pure antiandrogen Flutamide has been studied either alone or in combination with the LHRH agonist [D-Trp6, des-Gly-NH2(10)]LHRH ethylamide (LHRH-A), on testicular and prostatic functions in adult male rats. Treatment for 10 days with Flutamide (5 mg/rat, twice daily) caused a marked stimulation of plasma testosterone (T) associated with a significant increase in plasma gonadotropin concentrations and inhibited plasma PRL levels. Testicular weight is not changed following antiandrogen administration but testicular LH/hCG receptor levels are markedly decreased with no change in FSH receptor levels. Moreover, Flutamide treatment alone produces an important inhibition of ventral prostate and seminal vesicle weights associated with a significant decrease in prostatic beta-adrenergic receptor levels but no change is observed in specific ornithine decarboxylase (ODC) activity. Daily LHRH-A treatment at the dose of 1 microgram/day for 10 days decreases plasma T to levels comparable to those found in orchiectomized men (0.30 +/- 0.5 ng/ml). This effect is associated with an almost complete loss of testicular LH/hCG receptors, a decrease in testicular weight, a significant increase in plasma gonadotropins and a marked inhibition of plasma PRL concentration. A relatively smaller inhibition of ventral prostate and seminal vesicle weights follows treatment with the LHRH agonist alone, this effect being accompanied by a significant reduction in beta-adrenergic receptor concentration but no change in prostatic ODC activity. Combination of the two drugs, however, caused a potent inhibitory effect on both ventral prostate and seminal vesicle weight to values similar to those found in castrated rats. The prostatic weight loss is accompanied by a marked fall in ODC activity and in the concentration of beta-adrenergic receptors. The present data clearly show that combined treatment with an LHRH agonist and a pure antiandrogen is highly effective in inhibiting, not only prostatic growth, but also two androgen-sensitive parameters of prostatic activity.
Marchetti
B
B
MRC Group in Molecular Endocrinology, Laval University Medical Center, Québec, Canada.
Labrie
F
F
D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D005485:Flutamide / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011388:Prolactin / Q000097:blood; D011467:Prostate / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011962:Receptors, FSH / Q000378:metabolism; D011974:Receptors, LH / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000502:physiology*; D013739:Testosterone / Q000097:blood; D017329:Triptorelin Pamoate / Q000031:analogs & derivatives*
D000813:Anilides; D011943:Receptors, Adrenergic, beta; D011962:Receptors, FSH; D011974:Receptors, LH; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; C019176:Tryptal; D005485:Flutamide; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D009955:Ornithine Decarboxylase