Pituitary Desensitization with a Long-Acting Luteinizing-Hormone-Releasing Hormone Analog

A Potential New Treatment for Idiopathic Precocious Puberty
  • Gordon B. CutlerJr.
  • Florence Comite
  • Jean Rivier
  • Wylie W. Vale
  • D. Lynn Loriaux
  • William F. CrowleyJr.


Normal puberty appears to be initiated by the pulsatile secretion of luteinizing-hormone-releasing hormone (LHRH) from the hypothalamus at a frequency of about 1 pulse/hr (see Figure 1) (Boyar, Finkelstein, Roffwarg, Kapen, Weitzman, and Hellman, 1972; Knobil, 1980). The pulsatile secretion of LHRH stimulates secretion of the pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which in turn stimulate gonadal sex steroid secretion. The rise in the gonadal sex steroids estradiol and testosterone induces the secondary sexual changes at puberty.


Luteinizing Hormone Precocious Puberty Medroxyprogesterone Acetate LHRH Agonist Gonadal Dysgenesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Berquist, C., Nillius, S. J., and Wide, L. Intranasal gonadotropin-releasing hormone agonist as a contraceptive agent. Lancet, 1979, 2, 215–216.CrossRefGoogle Scholar
  2. Boume, G. A., Regiani, S., Payne, A. H., and Marshall, J. C. Testicular GnRH receptors—Characterization and localization on interstitial tissues. Journal of Clinical Endocrinology and Metabolism, 1980, 51, 407–409.CrossRefGoogle Scholar
  3. Boyar, R., Finkelstein, J., Roffwarg, H., Kapen, S., Weitzman, E., and Hellman, L. Synchronization of augmented luteinizing hormone secretion with sleep during puberty. New England Journal of Medicine, 1972, 287, 582–586.PubMedCrossRefGoogle Scholar
  4. Camacho, A. M., Williams, D. L., and Montalvo, J. M. Alterations of testicular histology and chromosomes in patients with constitutional sexual precocity treated with medroxyprogesterone acetate. Journal of Clinical Endocrinology and Metabolism, 1972, 34, 279–286.PubMedCrossRefGoogle Scholar
  5. Cargille, C. M., and Rayford, P. L. Characterization of antisera for human follicle stimulating hormone assay. Journal of Laboratory and Clinical Medicine, 1970, 75, 1030–1040.PubMedGoogle Scholar
  6. Clayton, R. N., Harwood, J. P., and Catt, K. J. Gonadotropin-releasing hormone analogue binds to luteal cells and inhibits progesterone production Nature, 1979, 282, 90–92.PubMedCrossRefGoogle Scholar
  7. Conte, F. A., Grumbach, M. M. and Kaplan, S. L. A diphasic pattern of gonadotropin secretion in patients with the syndrome of gonadal dysgenesis. Journal of Clinical Endocrinology and Metabolism, 1975, 40, 670–674.PubMedCrossRefGoogle Scholar
  8. Crowley, W. F., Vale, W., Beitins, I. Z., Rivier, J., Rivier, C. and McArthur, J. Chronic administration of a long-acting LRF agonist (D-Trp6-Pro9-NET-LRF), in hypogonadotropic hypogonadism: The critical nature of dosage and frequency in enhancement, extinction and restoration of gonadotropin responsiveness. Sixty-first Annual Meeting of the Endocrine Society, Los Angeles, June 1979, Abstract no. 16, p. 76.Google Scholar
  9. Crowley, W. F. Jr., Comite, F., Vale, W., Rivier, J., Loriaux, D. L., and Cutler, G. B. Jr. Therapeutic use of pituitary desensitization with a long-acting LHRH agonist: A potential new treatment for idiopathic precocious puberty. Journal of Clinical Endocrinology and Metabolism, 1981, 52, 370–372.PubMedCrossRefGoogle Scholar
  10. Dericks-Tan, J. S. E., Hammer, E., and Tauberg, H.-D. The effect of D-Ser-(TBU)6-LH-RHEA10 upon gonadotropin release in normally cyclic women. Journal of Clinical Endocrinology and Metabolism, 1977, 45, 597–600.PubMedCrossRefGoogle Scholar
  11. Dermody, W. C., and Reed, J. R. Effect of storage on LHRH. New England Journal of Medicine, 1976, 295, 173.PubMedGoogle Scholar
  12. Hsueh, A. T. W., and Erickson, F. G. Extra-pituitary action of gonadotropin-releasing hor- mone: Direct inhibition of ovarian steroidogenesis. Science, 1979, 204, 854–855.PubMedCrossRefGoogle Scholar
  13. Johnson, E. S., Gendrich, R. L., and White, W. F. Delay of puberty and inhibition of reproductive processes in the rat by a gonadotropin-releasing hormone agonist analog. Fertility and Sterility, 1976, 27, 853–860.PubMedGoogle Scholar
  14. Kaplan, S. A., Ling, S. M., and Irani, N. G. Idiopathic sexual precocity: Therapy with medroxyprogesterone. American Journal of Diseases of Children, 1968, 116, 591–598.PubMedGoogle Scholar
  15. Kelch, R. P., Kaplan, S. L., and Grumbach, M. M. Suppression of urinary and plasma follicle-stimulating hormone by exogenous estrogens in prepubertal and pubertal children. Journal of Clinical Investigation, 1973, 52, 1122–1128.PubMedCrossRefGoogle Scholar
  16. Knobil, E. The neuroendocrine control of the menstrual cycle. Recent Progress in Hormone Research, 1980, 36, 53–88.PubMedGoogle Scholar
  17. Loriaux, D. L., Ruder, H. J., and Lipsett, M. B. The measurement of estrone sulfate in plasma. Steroids, 1971, 18, 463–472.PubMedCrossRefGoogle Scholar
  18. Marshall, J. C., and Kelch, R. P. Low dose pulsatile gonadotropin-releasing hormone in anorexia nervosa: A model of human pubertal development. Journal of Clinical Endocrinology and Metabolism, 1979, 49, 712–718.PubMedCrossRefGoogle Scholar
  19. Mathews, J. H., Abrams, C. A. L., and Morishima, A. Pituitary-adrenal function in ten patients receiving medroxyprogesterone acetate for true precocious puberty. Journal of Clinical Endocrinology and Metabolism, 1970, 30, 653–658.PubMedCrossRefGoogle Scholar
  20. Meisels, A. That maturation value. Acta Cytologica, 1967, 11, 249–252.PubMedGoogle Scholar
  21. Odell, W. D., Rayford, P. L., and Ross, G. T. Simple, partially automated method for radioimmunoassay of human thyroid stimulating, growth, luteinizing and follicle stimulating hormone. Journal of Laboratory and Clinical Medicine, 1967a, 70, 973–980.PubMedGoogle Scholar
  22. Odell, W. D., Ross, G. T., and Rayford, P. L. Radioimmunoassay for luteinizing hormone in human plasma or serum: Physiological studies. Journal of Clinical Investigation, 1967b, 46, 248–255.PubMedCrossRefGoogle Scholar
  23. Ojeda, S. R., Andrews, W. W., Advis, J. P., and White, S. S. Recent advances in the endocrinology of puberty. Endocrine Reviews, 1980, 1, 228–257.PubMedCrossRefGoogle Scholar
  24. Petersen, A. C., and Taylor, B. The biological approach to adolescence: Biological change and psychological adaptation. In J. Adelson (Ed.), Handbook of adolescent psychology. New York: John Wiley and Sons, 1980, 117–155.Google Scholar
  25. Rabin, D., and McNeil, L. W. Pituitary and gonadal desensitization after continuous luteinizing hormone-releasing hormone infusion in normal females. Journal of Clinical Endocrinology and Metabolism, 1980, 51, 873–876.PubMedCrossRefGoogle Scholar
  26. Richman, R. A., Underwood, L. E., French, F. S., and Van Wyk, J. J. Adverse effects of large doses of medroxyprogesterone (MPA) in idiopathic isosexual precocity. Journal of Pediatrics, 1971, 79, 963–971.PubMedCrossRefGoogle Scholar
  27. Rifkind, A. B., Kulin, H. E., Cargille, C. M., Rayford, P. L., and Ross, G. T. Suppression of urinary excretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by medroxyprogesterone acetate. Journal of Clinical Endocrinology and Metabolism, 1969, 29, 506–513.PubMedCrossRefGoogle Scholar
  28. Rivier, C., Rivier, J., and Vale, W. Antireproductive effects of a potent gonadotropinreleasing hormone antagonist in the male rat. Science, 1980, 210, 93–95.PubMedCrossRefGoogle Scholar
  29. Ryan, K. D., and Foster, D. L. Neuroendocrine mechanisms involved in onset of puberty in the female: Concepts derived from the lamb. Federation Proceedings, 1980, 39, 2372–2377.PubMedGoogle Scholar
  30. Sadeghi-Nejad, A., Kaplan, S. L., and Grumbach, M. M. The effect of medroxyprogesterone acetate on adrenocortical function in children with precocious puberty. Journal of Pediatrics, 1971, 78, 616–624.PubMedCrossRefGoogle Scholar
  31. Sandow, J., von Rechenberg, W., Jerzabek, G., and Stoll, W. Pituitary gonadotropin inhibition by a highly active analog of luteinizing hormone-releasing hormone. Fertility and Sterility, 1978, 30, 205–209.PubMedGoogle Scholar
  32. Sizonenko, P. C. Endocrinology in preadolescents and adolescents. I. Hormonal changes during normal puberty. American Journal of Diseases of Children, 1978a, 132, 704–712.Google Scholar
  33. Sizonenko, P. C. Preadolescent and adolescent endocrinology: Physiology and physio-pathology. II. Hormonal changes during abnormal pubertal development. American Journal of Diseases of Children, 1978b, 132, 797–805.PubMedGoogle Scholar
  34. Styne, D. M., and Grumbach, M. M. Puberty in the male and female: Its physiology and disorders. In S. S. C. Yen, and R. Jaffee (Eds.), Reproductive endocrinology. Philadelphia: W. B. Saunders, 1978, 189–240.Google Scholar
  35. Tanner, J. M. Growth at adolescence. Oxford, England: Blackwell Scientific, 1978.Google Scholar
  36. Vale, W., Rivier, C., Brown, M., and Rivier, J. Pharmacology of thyrotropin releasing factor (TRF), luteinizing hormone releasing factor (LRH), and somatostatin. Advances in Experimental Medicine and Biology, 1977, 87, 123–156.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1983

Authors and Affiliations

  • Gordon B. CutlerJr.
    • 1
  • Florence Comite
    • 1
  • Jean Rivier
    • 2
  • Wylie W. Vale
    • 2
  • D. Lynn Loriaux
    • 1
  • William F. CrowleyJr.
    • 3
  1. 1.Developmental Endocrinology Branch, National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaUSA
  2. 2.Peptide Biology LaboratorySalk InstituteSan DiegoUSA
  3. 3.Vincent Research Laboratories, Departments of Internal Medicine and GynecologyMassachusetts General HospitalBostonUSA

Personalised recommendations