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Use of GnRH Antagonists as Physiologic Probes in the Female

  • Janet E. Hall
  • William F. CrowleyJr.
Conference paper
Part of the Serono Symposia, USA book series (SERONOSYMP)

Abstract

The development of GnRH antagonists has provided investigators studying reproductive hormones with unique opportunities that have not been available for the study of other hormonal systems. Although GnRH antagonists have been used to advantage in basic studies and in animal models, they are particularly important tools for clinical investigation because of the relatively restricted number of models with which basic physiologic and pathophysiologic questions can be addressed in the human and the additional opportunities that GnRH antagonists have afforded.

Keywords

Corpus Luteum GnRH Antagonist GnRH Analog GnRH Receptor GnRH Secretion 
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.

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References

  1. 1.
    Clayton RN, Catt KJ. Gonadotropin-releasing hormone receptors: characterization, physiological regulation and relationship to reproductive function. Endocr Rev 1981; 2: 186–209.PubMedCrossRefGoogle Scholar
  2. 2.
    Wynn PC, Suarez-Quian, Childs GV, Catt KJ. Pituitary binding and internalization of radioiodinated gonadotropin-releasing hormone agonist and antagonist ligands “in vitro” and “in vivo. ” Endocrinology 1986; 119: 1852–63.PubMedCrossRefGoogle Scholar
  3. 3.
    Karten MJ, Rivier JE. Gonadotropin-releasing hormone analog design: structure-function studies toward the development of agonists and antagonists: rationale and perspective. Endocr Rev 1986; 7: 44–66.PubMedCrossRefGoogle Scholar
  4. 4.
    Hall JE, Brodie TD, Badger TM, et al. Use of a gonadotropin releasing-hormone antagonist in the early follicular phase of the menstrual cycle: evidence of GnRH-independent FSH secretion. J Clin Endocrinol Metab 1988; 67: 534–53.CrossRefGoogle Scholar
  5. 5.
    Hall JE, Whitcomb RW, Rivier JE, Vale WW, Crowley WF Jr. Differential regulation of LH, FSH and free a-subunit secretion from the gonadotrope by GnRH: evidence from the use of two GnRH antagonists. J Clin Endocrinol Metab 1990; 70: 328–35.PubMedCrossRefGoogle Scholar
  6. 6.
    Hall JE, Bhatta N, Adams JM, Rivier JE, Vale WW, Crowley WF Jr. Variable tolerance of the developing follicle and corpus luteum to GnRH antagonist-induced gonadotropin withdrawal in the human. J Clin Endocrinol Metab 1991; 72: 993–1000.PubMedCrossRefGoogle Scholar
  7. 7.
    Hall JE, Crowley WF Jr. Use of a GnRH antagonist as a physiologic probe of GnRH secretion in women [Abstract]. In: Program of the 72nd annual meeting of The Endocrine Society, Atlanta, GA, 1990: 350.Google Scholar
  8. 8.
    Hall JE. The midcycle surge: quantity of GnRH secretion in the human, estimated by susceptibility to GnRH antagonism [Abstract]. In: Program of the 73rd annual meeting of The Endocrine Society, Washington, DC, 1991.Google Scholar
  9. 9.
    Hall JE, Taylor AE, Martin KA, Crowley WF Jr. Response of patients with polycystic ovarian disease to GnRH antagonist administration [Abstract]. Clin Res 1990; 38: 342A.Google Scholar
  10. 10.
    Crowley WF Jr, Beitins IZ, Vale WW, et al. The biologic activity of a potent analogue of gonadotropin-releasing hormone in normal and hypogonadotropic men. N Engl J Med 1980; 302: 1052–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Filicori M, Butler JP, Crowley WF. Neuroendocrine regulation of the corpus luteum in the human. J Clin Endocrinol Metab 1984; 73: 1638–47.Google Scholar
  12. 12.
    Whitcomb RW, Sangha JS, Schneyer AL, Crowley WF Jr. Improved measurement of free alpha subunit of glycoprotein hormones by,assay with use of a monoclonal antibody. Clin Chem 1988; 34: 2022–5.PubMedGoogle Scholar
  13. 13.
    Kourides IA, Weintraub BD, Ridgway EC, Maloof F. Pituitary secretion of free alpha and beta subunits of human thyrotropin in patients with thyroid disorders. J Clin Endocrinol Metab 1975; 40: 872–85.PubMedCrossRefGoogle Scholar
  14. 14.
    Kourides IA, Re RN, Weintraub BD, Ridgway EC, Maloof F. Metabolic clearance and secretion rates of subunits of human thyrotropin. J Clin Invest 1977; 77: 508–16.CrossRefGoogle Scholar
  15. 15.
    Whitcomb RW, O’Dea LSTL, Finkelstein JS, Heavern DM, Crowley WF Jr. Utility of free a-subunit as an alternative neuroendocrine marker of gonadotropin-releasing hormone (GnRH) stimulation of the gonadotroph in the human: evidence from normal and GnRH-deficient men. J Clin Endocrinol Metab 1990; 70: 1654–61.PubMedCrossRefGoogle Scholar
  16. 16.
    Schwall RH, Nikolics K, Szonyi E, Gorman C, Mason AJ. Recombinant expression and characterization of human activin A. Mol Endocrinol 1988; 2: 1237–42.PubMedCrossRefGoogle Scholar
  17. 17.
    Lumpkin MD, Moltz JH, Yu WH, Samson WK, McCann SM. Purification of FSH-releasing factor: its dissimilarity from LHRH of mammalian, avian, and piscian origin. Brain Res Bull 1987; 18: 175–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Dahl KD, Pavlou SN, Kovacs WJ, Hsueh AJW. The changing ratio of serum bioactive to immunoreactive follicle-stimulating hormone in normal men following treatment with a potent gonadotropin releasing hormone antagonist. J Clin Endocrinol Metab 1986; 63: 792–4.PubMedCrossRefGoogle Scholar
  19. 19.
    Clarke I. Exactitude in the relationship between GnRH and LH secretion. In: Crowley WF Jr, Conn PM, eds. Modes of action of GnRH and GnRH analogs. (See Chapter 11, this volume.)Google Scholar
  20. 20.
    Urban JH, Meredith JM, Bauer-Dantoin AC, Strobl FJ, Levine J. Gonadal feedback regulation of LHRH release and actions in the rat. In: Crowley WF Jr, Conn PM, eds. Modes of action of GnRH and GnRH analogs. (See Chapter 13, this volume.)Google Scholar
  21. 21.
    Caraty A, Bouchard P, Blane MR. Studies of LHRH secretion into the hypophyseal portal blood of the ram: gonadal regulation of LH secretion is mainly exerted at the hypothalamic level. In: Crowley WF Jr, Conn PM, eds. Modes of action of GnRH and GnRH analogs. (See Chapter 12, this volume.)Google Scholar
  22. 22.
    Karsch F, Moenter SM, Caraty A. The preovulatory surge of GnRH secretion: characterization and regulation. In: Crowley WF Jr, Conn PM, eds. Modes of action of GnRH and GnRH analogs. (See Chapter 15, this volume.)Google Scholar
  23. 23.
    Cicero TJ, Owens DP, Schmoeker PF, Meyer ER. Morphine-induced super-sensitivity to the effects of naloxone on luteinizing hormone secretion in the male rat. J Pharmacol Exp Ther 1983; 225: 35–41.PubMedGoogle Scholar
  24. 24.
    Ferin M, van Vugt D, Wardlaw S. The hypothalamic control of the menstrual cycle and the role of endogenous opioid peptides. Recent Prog Horm Res 1984; 40: 441–85.PubMedGoogle Scholar
  25. 25.
    Clayton RN, Solano AR, Garcia-Vela A, Dufau ML, Catt KJ. Regulation of pituitary receptors for gonadotropin-releasing hormone during the rat estrous cycle. Endocrinology 1980: 699–706.Google Scholar
  26. 26.
    Filicori M, Santoro N, Merriam GR, Crowley WF Jr. Characterization of the physiological pattern of episodic gonadotropin secretion throughout the human menstrual cycle. J Clin Endocrinol Metab 1986; 62: 1136–44.PubMedCrossRefGoogle Scholar
  27. 27.
    Hodgen GD. The dominant ovarian follicle. Fertil Steril 1982; 38: 281–300.PubMedGoogle Scholar
  28. 28.
    Fraser HM, Abbott M, Laird NC, McNeilly AS, Nestor JJ Jr, Bickery BH. Effects of an LH-releasing hormone antagonist on the secretion of LH, FSH, prolactin and ovarian steroids at different stages of the luteal phase in the stumptailed macaque (Maraca arctoides). J Endocrinol 1986; 111: 83–90.PubMedCrossRefGoogle Scholar
  29. 29.
    Hutchison JS, Zeleznik AJ. The corpus luteum of the primate menstrual cycle is capable of recovering from a transient withdrawal of pituitary gonadotropin support. Endocrinology 1985; 117: 1043–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Roseff SJ, Bangah ML, Kettel LM, et al. Dynamic changes in circulating inhibin levels during the luteal-follicular transition of the human menstrual cycle. J Clin Endocrinol Metab 1989; 69: 1033–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Mortola JF, Sathanandan M, Pavlou S, et al. Suppression of bioactive and immunoreactive follicle-stimulating hormone and luteinizing hormone levels by a potent gonadotropin-releasing hormone antagonist: pharmacodynamie studies. Fertil Steril 1989; 51: 957–63.PubMedGoogle Scholar
  32. 32.
    McLachlan RI, Cohen NL, Vale WW, et al. The importance of luteinizing hormone in the control of inhibin and progesterone secretion by the human corpus luteum. J Clin Endocrinol Metab 1989; 68: 1078–85.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 1992

Authors and Affiliations

  • Janet E. Hall
  • William F. CrowleyJr.

There are no affiliations available

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