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Journal of Andrology, Vol 1, Issue 5 209-228, Copyright © 1980 by The American Society of Andrology

Antifertility Effects of LHRH Agonists in the Male

FERNAND LABRIE 1, ALAIN BÉLANGER 1, LIONEL CUSAN 1, CARL SEGUIN 1, GEORGES PELLETIER 1, PAUL A. KELLY 1, JERRY J. REEVES 1, FLEUR-ANGE LEFEBVRE 1, ANDRE LEMAY 1, YVES GOURDEAU 1, AND JEAN-PIERRE RAYNAUD 2

1 Department of Molecular Endocrinology, Le Centre Hospitalier de l'Université Laval, Quebec, Canada
2 Centre de Recherches Roussel-UCLAF, Romainville, France

Acute or chronic treatment of adult male rats with LHRH or its agonists leads to a loss of testicular LH and prolactin receptors accompanied by decreased testis, seminal vesicle, and ventral prostate weight. The inhibition of testosterone formation is due to a blockage of the steroidogenic pathway at the level of 17-hydroxylase and 17,20-desmolase activities. The testicular desensitization is accompanied by a decreased pituitary responsiveness to LHRH. Although the inhibitory effects at the testicular level could be explained by endogenous LH release induced by the LHRH agonist with secondary testicular desensitization, the LH-releasing peptides also exert direct inhibitory effects on gonadotropin receptors at the testicular level. Moreover, LHRH and its agonists bind to a specific LHRH receptor in interstitial cells. Chronic treatment with LHRH agonists leads to marked degenerative changes in the seminiferous tubules, almost all tubules showing signs of histologic damage after four weeks of treatment. Single administration of an LHRH agonist by the intranasal route in normal adult men causes a transient inhibition of plasma testosterone levels with a temporary loss of diurnal cyclicity, whereas preliminary data obtained in patients with cancer of the prostate show inhibition of both testosterone and dihydrotestosterone plasma levels. Such data suggest the potential use of LHRH agonists in male contraception and for the treatment of cancer of the prostate.

     Key words: LHRH agonists, LH receptor, prolactin receptor, LHRH receptor, desensitization, spermatogenesis, intranasal, blockage of steroidogenesis

Submitted on March 17, 1980
Revised on May 18, 1980
Accepted on June 11, 1980






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Copyright © 1980 by The American Society of Andrology.