title: Characteristics of flutamide action on prostatic and testicular functions in the rat.
abstract: 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.
authors.affiliation: MRC Group in Molecular Endocrinology, Laval University Medical Center, Québec, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Marchetti
authors.forename: F
authors.initials: F
authors.lastname: Labrie
mesh_terms: 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*
chemical_list: 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