Characteristics of flutamide action on prostatic and testicular functions in the rat

J Steroid Biochem. 1988 Jun;29(6):691-8. doi: 10.1016/0022-4731(88)90170-7.

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.

MeSH terms

  • Anilides / pharmacology*
  • Animals
  • Flutamide / pharmacology*
  • Follicle Stimulating Hormone / blood
  • Gonadotropin-Releasing Hormone / analogs & derivatives
  • Gonadotropin-Releasing Hormone / pharmacology
  • Luteinizing Hormone / blood
  • Male
  • Orchiectomy
  • Organ Size / drug effects
  • Ornithine Decarboxylase / metabolism
  • Prolactin / blood
  • Prostate / drug effects
  • Prostate / physiology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, beta / metabolism
  • Receptors, FSH / metabolism
  • Receptors, LH / metabolism
  • Testis / drug effects
  • Testis / physiology*
  • Testosterone / blood
  • Triptorelin Pamoate* / analogs & derivatives*

Substances

  • Anilides
  • Receptors, Adrenergic, beta
  • Receptors, FSH
  • Receptors, LH
  • Triptorelin Pamoate
  • Gonadotropin-Releasing Hormone
  • Testosterone
  • Tryptal
  • Flutamide
  • Prolactin
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Ornithine Decarboxylase