Journal of Endocrinological Investigation

, Volume 5, Issue 6, pp 355–360 | Cite as

Sensitivity of luteinizing hormone and gonadal steroid responses to single intranasal administration of an LHRH agonist (Hoe-766) in young normal adult men

  • N. Faure
  • F. Labrie
  • A. Belanger
  • A. Lemay
  • J. P. Raynaud
  • M. Von Der Ohe
  • A. T. A. Fazekas


While intranasal administration of the potent LHRH agonist [D-Ser (TBL))6, des-Gly-NH2 10] LHRH ethylamide, Hoe-766,at the doses of 50 or 10μg, has little effect on serum LH levels, doses of 200, 500, 1250 or 2500μg cause a rapid and marked stimulation. A near-maximal effect is observed at 30 min with a 4- to 5-fold stimulation of serum LH concentration. A progressive increase of serum testosterone (T) levels is observed on the day of treatment with doses of 200μg and higher of the LHRH agonist with an effect lasting for 24 h at the 2 highest doses used. The increase of serum T levels at the 3 highest doses of Hoe-766 is followed by a decrease of androgen levels during the first throughout the third post treatment days. This temporary decrease of serum T levels is followed by a return to normal diurnal cyclicity and levels at later time intervals. An almost superimposable pattern is observed on serum 170H-progesterone levels: increase of serum levels lasting for up to 24 h followed by loss of diurnal cyclicity and low concentration during the first to third post treatment days. Plasma 17β-estradiol concentrations are increased for 48 h after administration of the two highest doses of Hoe-766 with a return to normal at later time intervals. The present data show that near-maximal stimulation of serum LH levels as well as 170H-progesterone, testosterone and 17β-estradiol secretion can be achieved by doses of Hoe-766 ranging between 200 and 500μg by the intranasal route. Moreover, doses of Hoe-766 leading to a stimulation of LH and androgen secretion cause a transient loss of diurnal cyclicity and low levels of circulating T and 170H-progesterone lasting for one to three days with a complete return to normal at later time intervals. It is thus suggested that intranasal doses of Hoe-766 ranging from 200 to 500μg could be used chronically to inhibit androgen secretion in men for treatment of androgen dependent diseases such as cancer of the prostate and benign prostatic hyperplasia.


LHRH agonist testicular steroids diurnal variation progesterone 17OH-progesterone desensitization 


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  1. 1.
    Auclair C., Kelly P.A., Labrie F., Coy D.H., Schally A.V. Inhibition of testicular LH/hCG receptor level by treatment with a potent LHRH agonist or hCG. Biochem. Biophys. Res. Commun. 76: 855, 1977.PubMedCrossRefGoogle Scholar
  2. 2.
    Labrie F., Auclair C., Cusan L, Kelly P.A., Pelletier G., Ferland L. Inhibitory effects of LHRH and its agonists on testicular gonadotropin receptors and spermatogenesis in the rat. Int. J. Androl. (Suppl. 2): 303, 1978.Google Scholar
  3. 3.
    Sandow J., Von Rechenberg W.V., Konig W., Hahn M., Jerzabek G., Fraser H. Physiological studies with highly active analogues of LHRH. In.Gupta D., Voelter W. (Eds.), Hypoyhalamic hormones-chemistry, physiology and clinical applications. Verlag Chimie, 1978, p. 307.Google Scholar
  4. 4.
    Sandow J., Von Rechenberg W., Jerzabek G., Stoll W. Pituitary gonadotropin inhibition by a highly active analog of luteinizing hormone-releasing hormone. Fertil. Steril. 30: 205, 1978.PubMedGoogle Scholar
  5. 5.
    Rivier C., Rivier J., Vale W. Chronic effects of [D-Trp6, Pro9, NET] luteinizing hormone-releasing factor on reproductive processes in the male rat. Endocrinology 105: 1191, 1979.PubMedCrossRefGoogle Scholar
  6. 6.
    Catt. K.J., Baukal A.J., Davies T.F., Dufau M.L Luteinizing hormone-releasing hormone-induced regulation of gonadotropin and prolactin receptors in the rat testis. Endocrinology 104: 17, 1979.PubMedCrossRefGoogle Scholar
  7. 7.
    Belanger A., Auclair C., Seguin C., Kelly P.A., Labrie F. Down-regulation of testicular androgen biosynthesis and LH receptor levels by an LHRH agonist: role of prolactin. Mol. Cell. Endocrinol. 13: 47, 1979.PubMedCrossRefGoogle Scholar
  8. 8.
    Belanger A., Auclair C., Ferland L., Labrie F. Time course of the effects of treatment with a potent LHRH agonist on testicular steroidogenesis and gonadotropin receptor levels in the adult rat. J. Steroid Biochem. 13: 191, 1980.PubMedCrossRefGoogle Scholar
  9. 9.
    Belanger A., Labrie F., Lemay A., Caron S., Raynaud J.P. Inhibitory effects of a single intranasal administration of [D-Ser (TBU)6, des-Gly-NH2 10] LHRH agonist, on serum steroid levels in normal adult men. J, Steroid Biochem. 13:123, 1980.CrossRefGoogle Scholar
  10. 10.
    Labrie F., Belanger A., Cusan L., Seguin C., Pelletier G., Kelly P.A., Reeves J.J., Lefebvre F.A., Lemay A., Raynaud J.P. Antifertility effects of LHRH agonist in the male. J. Androl. 1: 209, 1980.Google Scholar
  11. 11.
    Belanger A., Caron S., Picard V. Simultaneous radioimmunoassay of progestin, androgen and estrogen in adult rat testis. J. Steroid Biochem. 13: 1865, 1979.Google Scholar
  12. 12.
    Rodbard D., Lewald J.E. Computer analysis of radioligand assay and radioimmunoassay data. In: Diczfalusy E. (Ed.), Second Karolinska Symposium on Research Methods in Reproductive Endocrinology. Bogtryheiret Forum, Copenhagen, 1970, p. 79.Google Scholar
  13. 13.
    Kramer C.Y. Extension of multiple-range tests to group means with unique numbers of replications. Biometrics 12: 307, 1956.CrossRefGoogle Scholar
  14. 14.
    Carmichael R., Belanger A., Cusan L, Seguin C, Caron S., Labrie F. Increased testicular androstane-3α17β-diol formation induced by treatment with [D-Ser (TBU)6, des-Gly-NH2 10] LHRH-ethylamide in the rat. Steroids (in press).Google Scholar
  15. 15.
    Smith R., Donald R.A., Espiner E.A., Stromach S.G., Edwards I.A. Normal adults and subjects with hypogonadotropic hypogonadism respond differently to [D-Ser (TBU)6,des-Gly-NH2 10] LHRH-EA. J. Clin. Endocrinol. Metab. 48: 167, 1979.PubMedCrossRefGoogle Scholar
  16. 16.
    Bergquist C., Nillius S.J., Bergh T., Skarin G., Wide L Inhibitory effects on gonadotrophin secretion and gonadal function in men during chronic treatment with a potent stimulatory luteinizing hormone-releasing hormone analogue. Acta Endocrinol. (Kbh.), 91: 601, 1979.Google Scholar
  17. 17.
    Cusan L., Auclair C., Belanger A., Ferland L., Kelly P.A., Seguin C., Labrie F. Inhibitory effects of long-term treatment with an LHRH agonist on the pituitary-gonadal axis in male and female rats. Endocrinology 104: 1369, 1979.PubMedCrossRefGoogle Scholar
  18. 18.
    Arimura A., Serafini P., Talbot S., Schally A.V. Reduction of testicular luteinizing hormone/ human chorionic gonadogropin receptors by [D-Trp6]-luteinizing hormone-releasing hormone in hypophysectomized rats. Biochem. Biophys. Res. Commun. 90: 687, 1979.PubMedCrossRefGoogle Scholar
  19. 19.
    Hsueh A.J.W., Erickson G.F. Extra-pituitary inhibition of testicular function by luteinizing hormone-releasing hormone. Nature 281: 66, 1979.PubMedCrossRefGoogle Scholar
  20. 20.
    Lefebvre F.A., Reeves J.J., Seguin C., Massicotte J., Labrie F. Specific binding of a potent LHRH agonist in rat testis. Mol. Cell. Endocrinol. 20: 127, 1980.PubMedCrossRefGoogle Scholar
  21. 21.
    Sharpe R.M., Fraser H.M. Leydig cell receptors for luteinizing hormone-releasing hormone and its agonists and their modulation by administration or deprivation of the releasing hormone. Biochem. Biophys. Res. Commun. 95: 256, 1980.PubMedCrossRefGoogle Scholar
  22. 22.
    Bourne G.A., Regiani S., Payne A.H., Marshall J.C. Testicualr GnRH receptors. Characterization and localization on interstitial tissue. J. Clin. Endocrinol. Metab. 51: 407, 1980.PubMedCrossRefGoogle Scholar
  23. 23.
    Sharpe R.M., Fraser H.M. hCG stimulation of testicular LHRH-like activity. Nature 287: 642, 1980.PubMedCrossRefGoogle Scholar
  24. 24.
    Pelletier G., Cusan L., Auclair C., Kelly P.A., Desy L., Labrie F. Inhibition of spermatogenesis in the rat by treatment with [D-Ala6, des-Gly-NH2 10] LHRH ethylamide. Endocrinology 103: 641, 1978.PubMedCrossRefGoogle Scholar
  25. 25.
    Seguin C., Cusan L., Belanger A., Kelly P.A., Labrie F., Raynaud J.P. Marked inhibitory effects of the combined administration of a potent LHRH agonist and a non-steroidal antiandrogen on androgen secretion and action. Mol. Cell. Endocrinol. (In press).Google Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 1982

Authors and Affiliations

  • N. Faure
    • 1
  • F. Labrie
    • 2
  • A. Belanger
    • 2
  • A. Lemay
    • 1
  • J. P. Raynaud
    • 3
  • M. Von Der Ohe
    • 4
  • A. T. A. Fazekas
    • 5
  1. 1.Laboratory of Endocrinology of ReproductionSt. François d’Assise HospitalQuébecCanada
  2. 2.Department of Molecular EndocrinologyLe Centre Hospitalier de l’Université de LavalQuébecCanada
  3. 3.Centre de Recherches Roussel UCLAFRomainvilleFrance
  4. 4.Medical DepartmentHoechst AGFrankfurt/MainFederal Republic of Germany
  5. 5.Medical DepartmentHoechst CanadaMontrealCanada

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