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Reversibility of GnRH Agonist-Induced Inhibition of Testicular Function: Comparison Between Rat, Monkey and Man

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LH-RH Agonists in Oncology

Abstract

Gonadotropin-releasing hormone (GnRH) agonists and antagonists bind to hypophyseal GnRH receptors and thereby inhibit gonadotropin release (Nestor et al. 1984). However, the mechanism of blocking gonadotropin release for GnRH agonists is different from that for antagonists. GnRH agonists initially stimulate LH and FSH secretion, but this is quickly followed by a down-regulation of pituitary GnRH receptors. The GnRH-agonist-receptor complex is internalized by the gonadotropic cells (Duello et al. 1983) and decreased secretion of gonadotropic hormones results (Loumaye and Catt 1983). In contrast, GnRH antagonists bind firmly to the GnRH receptor and inhibit gonadotropin synthesis and release by blocking the action of hypothalamic GnRH (Heber et al. 1982; Loumaye et al. 1984). As a consequence of the induced hypogonadotropism, testosterone production is decreased and chronic treatment with GnRH analogues severely impairs or completely suppresses spermatogenesis in primates (Weinbauer and Nieschlag 1985) and rats (Labrie et al. 1980). Since rat Ley dig cells have receptors for GnRH agonists, additional direct effects of the GnRH analogues on the testes of this species have been considered (Cao et al. 1982; Hsueh et al. 1983).

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References

  • Adams LA, Bremner WJ, Nestor JJ jr. Vickery BH, Steiner R (1986) Suppression of plasma gonadotropins and testosterone in adult male monkeys (Macaca fascicularis) by a potent inhibitory analog of gonadotropin-releasing hormone. J Clin Endocrinol Metab 62: 58–63

    Article  PubMed  CAS  Google Scholar 

  • Akhtar FB, Marshall GR, Wickings EJ, Nieschlag E (1983 a) Reversible induction of azoospermia in rhesus monkeys by constant infusion of a GnRH agonist using osmotic minipumps. J Clin Endocrinol Metab 56: 534–540

    Article  PubMed  CAS  Google Scholar 

  • Akhtar FB, Marshall GR, Nieschlag E (1983b) Testosterone supplementation attenuates the antifertility effects of an LH-RH agonist in male monkeys. Int J Androl 6: 461–468

    Article  PubMed  CAS  Google Scholar 

  • Akhtar FB, Wickings EJ, Nieschlag E (1984) Male fertility control with an LH-RH agonist: primate studies. In: Vickery BH, Nestor JJ jr, Hafez ESE (eds) LH-RH and its analogs. MTP Press, Lancaster, pp 77–90

    Chapter  Google Scholar 

  • Akhtar FB, Weinbauer GF, Nieschlag E (1985) Acute and chronic effects of a gonadotrophin-releasing hormone antagonist on pituitary and testicular function in monkeys. J Endocrinol 104: 345–354

    Article  CAS  Google Scholar 

  • Asch RH, van Sickle M, Rettori V, Balmaceda JP, Eddy CA, Coy DH, Schally AV (1981) Absence of LH-RH binding sites in corpora lutea from rhesus monkeys (Macaca mulatto). J Clin Endocrinol Metab 53: 215–217

    Article  PubMed  CAS  Google Scholar 

  • Bambino TH, Schreiber JR, Hsueh AJW (1980) Gonadotropin-releasing hormone and its agonist inhibit testicular luteinizing hormone receptor and steroidogenesis in immature and adult hypophysectomized rats. Endocrinology 107: 908–917

    Article  PubMed  CAS  Google Scholar 

  • Barham SS, Berlin JD (1974) Fine structure and cytochemistry of testicular cells in men treated with testosterone propionate. Cell Tissue Res 148: 159 - 182

    Article  PubMed  CAS  Google Scholar 

  • Bergh A, Widmark A, Damber JE, Cajander S (1986) Are leukocytes involved in the human chorionic gonadotropin-induced increase in testicular vascular permeability? Endocrinology 119: 586–590

    Article  PubMed  CAS  Google Scholar 

  • Bergquist C, Nillius SJ, Bergh T, Skarin G, Wide C (1979) Inhibitory effects on gonadotropin secretion and gonadal function in men during chronic treatment with a potent stimulatory luteinizing hormone-releasing hormone analogue. Acta Endocrinol (Copenh) 91: 601–609

    CAS  Google Scholar 

  • Bex FJ, Corbin A (1981) In vivo and in vitro investigation of the extrapituitary antireproductive effects of a potent LH-RH agonist in immature and adult male rats. J Androl 3: 152–161

    Google Scholar 

  • Bex FJ, Corbin A (1982) Resistance of the mouse to the antifertility effects of LH-RH agonists. Life Sci 30: 1263–1269

    Article  PubMed  CAS  Google Scholar 

  • Bhasin S, Heber D, Steiner BS, Handelman DJ, Swerdloff RS (1985) Hormonal effects of gonadotropin-releasing hormone (GnRH) agonist in the human male. III. Effects of long-term combined treatment with GnRH agonist and androgen. J Clin Endocrinol Metab 60: 998–1003

    Article  PubMed  CAS  Google Scholar 

  • Bouchard P, Blondet C, Spitz I, Brailly S, Jouannet P, Schaison G (1986) Sperm suppression by long-acting GnRH agonist therapy in men: critical effect of testosterone substitution and duration of therapy. 68th Meeting Endocrine Society, Anaheim, Calif., USA (Abstract No. 498)

    Google Scholar 

  • Cao YC, Sundaram K, Bardin CW, Rivier J, Vale W (1982) Direct inhibition of testicular steroidogenesis and gonadotropin receptor levels by (im Bzl)-D-His6-Pro9-NEt) GnRH and (D-Trp6, Pro9-NEt) GnRH, potent agonists of GnRH. Int J Androl 5: 158–170

    Article  PubMed  CAS  Google Scholar 

  • Cassorla F, Renquist D, Barnard D, Munabi AK, Cutler GB jr, Loriaux DL (1984) Effects of luteinizing hormone-releasing hormone (LH-RH) analog D-Trp6-Pro9-NEt-LH-RH on the pituitary-gonadal axis of prepubertal rhesus monkeys. Biol Reprod 30: 1130–1134

    Article  PubMed  CAS  Google Scholar 

  • Clayton R, Huhtaniemi I (1982) Absence of gonadotropin-releasing hormone receptors in human gonadal tissue. Nature 299: 56–59

    Article  PubMed  CAS  Google Scholar 

  • Comité F, Cutler GB jr, Loriaux DL (1984) LH-RH analog therapy of precocious puberty. In: Vickery BH, Nestor JJ jr, Hafez ESE (eds) LH-RH and its analogs. MTP Press, Lancaster, pp 315–328

    Chapter  Google Scholar 

  • Crowley WF, Comité F, Vale WW, Rivier J, Loriaux DL, Cutler GB (1981) Therapeutic use of pituitary desensitisation with a long-acting GnRH agonist: a potential new treatment for idiopathic precocious puberty. J Clin Endocrinol Metab 52: 370–372

    Article  PubMed  Google Scholar 

  • Dahl KD, Pavlou SN, Kovacs WJ, Hsueh AJW (1986) The changing ratio of serum bioactive to immunoreactive follicle-stimulating hormone in normal men following treatment with gonadotropin releasing hormone antagonist. J Clin Endocrinol Metab 63: 792–794

    Article  PubMed  CAS  Google Scholar 

  • Damber JE, Bergh A, Daehlin L (1984) Effect of an LH-RH-agonist on testicular blood flow in hypophysectomized rats. Int J Androl 7: 236–243

    Article  PubMed  CAS  Google Scholar 

  • Doelle GC, Alexander AN, Evans RM, Linde R, Rivier J, Vale W, Rabin D (1983) Combined treatment with an LH-RH-agonist and testosterone in man. J Androl 4: 298–302

    PubMed  CAS  Google Scholar 

  • Duello TM, Nett TM, Farquhar MG (1983) Fate of gonadotropin-releasing hormone agonist internalized by rat pituitary gonadotropes. Endocrinology 112: 1–10

    Article  PubMed  CAS  Google Scholar 

  • Dym M, Madhwra Raj HG (1977) Response of adult rat Sertoli cells and Leydig cells to depletion of luteinizing hormone and testosterone. Biol Reprod 17: 676–696

    Article  PubMed  CAS  Google Scholar 

  • Edgren RA, Shevlin DR (1984) The therapeutic potential of LH-RH and LH-RH analogs. In: Vickery BH, Nestor JJ jr, Hafez ESE (eds) LH-RH and its analogs. MTP Press, Lancaster, pp 449–458

    Chapter  Google Scholar 

  • Evans RM, Doelle GC, Alexander AN, Uderman HD, Rabin D (1984) Gonadotropin and steroid secretory patterns during chronic treatment with a luteinizing hormone-releasing hormone agonist analog in men. J Clin Endocrinol Metab 58: 862–867

    Article  PubMed  CAS  Google Scholar 

  • Flickinger CJ (1978) Effects of testosterone enanthate on the structure of the male reproductive tract of the rat. Anat Ree 192: 555–584

    Article  CAS  Google Scholar 

  • Fraser HM (1982) Antifertility effects of GnRH. J Reprod Fertil 64: 503–515

    Article  PubMed  CAS  Google Scholar 

  • Frick J, Aulitzky W (1986) Effects of a potent LH-RH-agonist on the pituitary gonadal axis with and without testosterone substitution. Urol Res 14: 261–264

    Article  PubMed  CAS  Google Scholar 

  • Habenicht UF, El Etreby MF, Neumann F (1985) Possible vascular effects of an LH-RH agonist on the peripheral circulation of the rat testis. Andrologia 17: 440–443

    Article  PubMed  CAS  Google Scholar 

  • Handelsman DJ, Staraj S (1985) Testicular size: the effects of aging, malnutrition and illness. J Androl 6: 144–151

    PubMed  CAS  Google Scholar 

  • Heber D, Dodson R, Swerdloff RS (1982) Pituitary receptor site blockade by a gonadotropin-releasing hormone antagonist in vivo: mechanism of action. Science 216: 420–421

    Article  PubMed  CAS  Google Scholar 

  • Holstein AF, Hubmann R (1981) Spermatogonia in old age. In: Holstein AF, Schirren C (eds) Stem cells in spermatogenesis. Grosse Verlag, Berlin, pp 77–88

    Google Scholar 

  • Hsueh AJW, Erickson GF (1978) Extra-pituitary inhibition of testicular function by luteinizing hormone releasing hormone. Nature 281: 66–67

    Article  Google Scholar 

  • Hsueh AJW, Schreiber JR, Erickson GF (1981) Inhibitory effect of gonadotropin releasing hormone upon cultured testicular cells. Mol Cell Endocrinol 21: 43–49

    Article  PubMed  CAS  Google Scholar 

  • Hsueh AJW, Bambino TH, Zhuang LZ, Welsh TH jr, Ling NC (1983) Mechanism of the direct action of gonadotropin-releasing hormone and its antagonist on androgen biosynthesis by cultured rat testicular cells. Endocrinology 112: 1653–1661

    Article  PubMed  CAS  Google Scholar 

  • Huhtaniemi IT, Nero N, Amsterdam A, Naor Z (1986) Effect of postnatal treatment with a gonadotropin-releasing hormone antagonist on sexual maturation of male rats. Biol Reprod 35: 501–507

    Article  PubMed  CAS  Google Scholar 

  • Huhtaniemi IT, Nikula H, Detta A, Stewart JM, Clayton RN (1987) Blockade of rat testicular gonadotropin releasing hormone ( GnRH) receptors by infusion of a GnRH antagonist has no major effects on Leydig cell function in vivo. Mol Cell Endocrinol 49: 89–97

    Article  PubMed  CAS  Google Scholar 

  • Hunter MG, Sullivan MHF, Dix CJ, Aldred LF, Cooke BA (1982) Stimulation and inhibition by LH- RH analogues of cultured rat Leydig cell function and lack of effect on mouse Leydig cells. Mol Cell Endocrinol 27: 31–44

    Article  PubMed  CAS  Google Scholar 

  • Johnson L, Petty CS, Neaves WB (1984) Influences of age on sperm production and testicular weights in men. J Reprod Fertil 70: 211–218

    Article  PubMed  CAS  Google Scholar 

  • Karten MJ, Rivier JE (1986) Gonadotropin-releasing hormone analog design. Structure-function studies toward the development of agonist and antagonist: rationale and perspective. Endocr Rev 7: 44–66

    Article  PubMed  CAS  Google Scholar 

  • Kauli R, Pertzelan A, Ben-Jeer Z, Prager-Lewin R, Kaufman H, Comaru-Schally AM, Schally AV, Laron Z (1984) Treatment of precocious puberty with LH-RH analogue in combination with cyprbterone acetate — further experience. Clin Endocrinol (Oxf) 20: 377–387

    Article  CAS  Google Scholar 

  • Kothari LK, Gupta AS (1974) Effect of aging on the volume, structure and total Ley dig cell content of the human testis. Int J Fertil 19: 140–146

    PubMed  CAS  Google Scholar 

  • Kroonenburgh MJPG van, Beck JL, Vemer HM, Rolland R, Thomas CMG, Herman CJ (1986) Effects of a single injection of a new depot formulation of an LH-releasing hormone agonist on spermatogenesis in adult rats. J Endocrinol 11: 449–454

    Article  Google Scholar 

  • Labrie F, Belanger A, Cusan L, Seguin C, Pelletier G, Kelly PA, Reeves JJ, Lefebrve FA, Lomay A, Gourdeau Y, Raynaud JP (1980) Antifertility effects of LH-RH agonists in the male. J Androl 1: 209–228

    CAS  Google Scholar 

  • Lefebrve FA, Reeves JJ, Seguin C, Massicotte, Labrie F (1980) Specific binding of a potent LH-RH agonist in rat testis. Mol Cell Endocrinol 20: 127–134

    Article  Google Scholar 

  • Lefebrve FA, Belanger A, Pelletier G, Labrie F (1984) Recovery of gonadal functions in the adult male rat following cessation of five months daily treatment with an LH-RH agonist. J Androl 5: 181–192

    Google Scholar 

  • Limonta P, Bardin CW, Ladishenskaya A, Pavlou S, Sundaram K, Thau RB (1985) Species differences in the sensitivity to a GnRH antagonist. Contraception 32: 75–85

    Article  PubMed  CAS  Google Scholar 

  • Linde R, Doelle GC, Alexander N, Kirchner F, Vale W, Rivier J, Rabin D (1981) Reversible inhibition of testicular steroidogenesis and spermatogenesis by a potent gonadotropin-releasing hormone agonist in normal men. N Engl J Med 305: 663–667

    Article  PubMed  CAS  Google Scholar 

  • Loumaye E, Catt KJ (1983) Agonist-induced regulation of pituitary receptors for gonadotropin-releasing hormone. J Biol Chem 258: 12002–12009

    PubMed  CAS  Google Scholar 

  • Loumaye E, Wynn PC, Coy D, Catt KJ (1984) Receptor-binding properties of gonadotropin- releasing hormone derivatives. J Biol Chem 259: 12663–12671

    PubMed  CAS  Google Scholar 

  • Mann DR, Davis-DaSilva M, Wallen K, Coan P, Evans DE, Collins DC (1984a) Blockade of neonatal activation of the pituitary-testicular axis with continuous administration of a gonadotropin-releasing hormone agonist in male rhesus monkeys. J Clin Endocrinol Metab 59: 207–211

    Article  PubMed  CAS  Google Scholar 

  • Mann DR, Gould KG, Collins DC (1984b) Influence of continuous gonadotropin-releasing hormone ( GnRH) agonist treatment on luteinizing hormone and testosterone secretion, the response to GnRH, and the testicular response to human chorionic gonadotropin in male rhesus monkeys. J Clin Endocrinol Metab 58: 262–267

    Article  PubMed  CAS  Google Scholar 

  • Mann DR, Smith MM, Gould KG, Collins DC (1985) Effect of a gonadotropin-releasing hormone agonist on luteinizing hormone and testosterone secretion and testicular histology in male rhesus monkeys. Fertil Steril 43: 115–121

    PubMed  CAS  Google Scholar 

  • Marshall GR, Jockenhövel F, Lüdecke D, Nieschlag E (1986) Maintenance of complete but quantitatively reduced spermatogenesis in hypophysectomized monkeys by testosterone alone. Acta Endocrinol (Copenh) 113: 424–431

    CAS  Google Scholar 

  • Michel E, Bents H, Akhtar FB, Hönigl W, Knuth UA, Sandow J, Nieschlag E (1985) Failure of high-dose sustained release luteinizing hormone releasing hormone agonist ( Buserelin) plus oral testosterone to suppress male fertility. Clin Endocrinol (Oxf) 23: 663–675

    Article  CAS  Google Scholar 

  • Nestor JJ jr, Ho TL, Tahilramani R, Horner BL, Simpson RA, Jones GH, McRae Gl, Vickery BH (1984) LH-RH agonists and antagonists containing very hydrophobic amino acids. In: Vickery BH, Nestor JJ jr, Hafez ESE (eds) LH-RH and its analogs. MTP Press, Lancaster, pp 23–34

    Chapter  Google Scholar 

  • Nieschlag E, Michel E (1986) Reproductive functions in grandfathers. In: Mastroianni JL jr, Paulsen CA (eds) Aging, reproduction, and the climacteric. Plenum, New York, pp 59–71

    Google Scholar 

  • Nieschlag E, Wickings EJ (1980) Does the rhesus monkey provide a suitable model for human testicular function? In: Serio M, Martini L (eds) Animal models in human reproduction, Raven Press, New York, pp 151–159

    Google Scholar 

  • Nieschlag E, Michel E, Weinbauer G (1986) Preclinical and clinical trials with LH-RH agonists and antagonists. In: Zatuchni GI, Goldsmith A, Spieler JM, Sciarra J J (eds) Male contraception. Advances and future prospects. Harper and Row, Philadelphia, pp 369–375

    Google Scholar 

  • Pavlou SN, Debold CR, Island DP, Wakefield G, Rivier J, Vale W, Rabin D (1986) Single subcutaneous doses of a luteinizing hormone-releasing hormone antagonist supress serum gonadotropin and testosterone levels in normal men. J Clin Endocrinol Metab 63: 303–308

    Article  PubMed  CAS  Google Scholar 

  • Pelletier G, Cusan L, Auclair C, Kelly PA, Desy L, Labrie F (1978) Inhibition of spermatogenesis in the rat by treatment with (D-Ala6, des-Gly NH210) LH-RH Ethylamide. Endocrinology 103: 641–643

    Article  PubMed  CAS  Google Scholar 

  • Pelletier G, Cusan GL, Belanger A, Seguin A, Kelly PA, Labrie F (1980) Further studies on the inhibitory effect of (D-Ala6, des-Gly-NH210) LH-RH ethylamide on spermatogenesis and steroidogenesis in the rat. J Androl 1: 171–181

    CAS  Google Scholar 

  • Pineda JL, Lee BC, Spiliotis BE, Vale W, Rivier J, Brown TJ, Bereu BB (1983) Effect of a GnRH antagonist, (Ac-AVPro1, pF-Phe2, D-Trp3,6) GnRH on pulsatile gonadotropin secretion in the castrate male primate. J Clin Endocrinol Metab 56: 420–422

    Article  PubMed  CAS  Google Scholar 

  • Rabin D, Evans RM, Alexander AN, Doelle GC, Rivier J, Vale W, Liddle G (1984) Heterogeneity of sperm density profiles following 20-week therapy with high-dose LH-RH analog plus testosterone. J Androl 5: 176–180

    PubMed  CAS  Google Scholar 

  • Rajfer J, Swerdloff RS, Heber DM (1984) Testicular histology following chronic gonadotrophin-releasing hormone agonist treatment. Fertil Steril 42: 765–771

    PubMed  CAS  Google Scholar 

  • Rajfer J, Sikka SC, Swerdloff RS (1987) Lack of a direct effect of gonadotropin hormone-releasing hormone agonist on human testicular steroidogenesis. J Clin Endocrinol Metab 64: 62–67

    Article  PubMed  CAS  Google Scholar 

  • Rea MA, Marshall GR, Weinbauer GF, Nieschlag E (1986) Testosterone maintains pituitary and serum FSH and spermatogenesis in GnRH antagonist-suppressed rats. J Endocrinol 108: 101–107

    Article  PubMed  CAS  Google Scholar 

  • Rea MA, Weinbauer GF, Marshall GR, Nieschlag E (1987) Testosterone stimulates pituitary and serum FSH in GnRH antagonist-suppressed rats. Acta Endocrinol (Copenh) 113: 487–492

    Google Scholar 

  • Rivier C, Rivier J, Vale W (1979) Chronic effects of (D-Trp6, Pro9-NEt) luteinizing hormone- releasing hormone factor on reproductive processes in the male rat. Endocrinology 106: 1191–1201

    Article  Google Scholar 

  • Rivier C, Rivier J, Vale W (1980) Effect of a potent GnRH antagonist and testosterone proprionate on mating behavior and fertility in the male rat. Endocrinology 108: 1998–2001

    Article  Google Scholar 

  • Rivier C, Rivier J, Vale W (1981) Antireproductive effects of a potent gonadotropin-releasing hormone antagonist in the male rat. Science 210: 93–95

    Article  Google Scholar 

  • Sandow J, von Rechenberg W, Jerzabek G, Engelbart K, Kuhl H, Fraser H (1980) Hypothalamic-pituitary-testicular function in rats after supraphysiological doses of a highly active LH-RH analogue (Buserelin). Acta Endocrinol (Copenh) 94: 489–497

    CAS  Google Scholar 

  • Sandow J, Beier B, Jerzabek-Sandow G, Klante G, Engelbart K (1984) Androgen biosynthesis in male rats under long-term treatment with an LH-RH-agonist (Buserelin). 3rd Joint Meeting of the British Endocrine Societies, Edinburgh, Abstract No. 57

    Google Scholar 

  • Sandow J, von Rechenberg W, Stoll W, Klante G (1985a) Inhibitory effects of acute gonadotrophin stimulation on the reproductive system of male rats. Acta Endocrinol [Suppl] (Copenh) 267: 183

    Google Scholar 

  • Sandow J, Engelbart K, von Rechenberg W (1985b) The different mechanisms for suppression of pituitary and testicular function. Med Biol 63: 192–200

    CAS  Google Scholar 

  • Schaison G, Brailly S, Vuagnat P, Bouchard P, Milgrom E (1984) Absence of a direct inhibitory effect of the gonadotrophin-releasing hormone (GnRH) agonist, D-Ser(tBU)6,des-Gly-NH(2)10-Ethyl-amide ( Buserelin) on testicular steroidogenesis in men. J Clin Endocrinol Metab 58: 885–888

    Article  PubMed  CAS  Google Scholar 

  • Schürmeyer T, Knuth UA, Freischem CW, Sandow J, Akhtar FB, Nieschlag E (1984) Suppression of pituitary and testicular function in normal men by constant gonadotrophin-releasing hormone agonist infusion. J Clin Endocrinol Metab 59: 1–6

    Article  Google Scholar 

  • Séguin C, Bélanger A, Cusan L, Pelletier G, Reeves JJ, Lefebrve FA, Kelly PA, Labrie F (1981) Relative Importance of the adenohypophyseal and gonadal sites of inhibitory action of LH-RH agonists. Biol Reprod 24: 889–901

    Article  PubMed  Google Scholar 

  • Séguin C, Belanger A, Labrie F, Hansel W (1982) Study of the direct action of the luteinizing hormone-releasing hormone agonists at the testicular level in intact rats treated with an antiluteinizing hormone serum. Endocrinology 110: 524–530

    Article  PubMed  Google Scholar 

  • Sharpe RM (1976) hCG-induced decrease in availability of rat testis receptors. Nature 264: 644–645

    Article  PubMed  CAS  Google Scholar 

  • Sharpe RM (1984) Intratesticular factors controlling testicular function. Biol Reprod 30: 29–49

    Article  PubMed  CAS  Google Scholar 

  • Smith jr JA, Urry RL (1985) Testicular histology after prolonged treatment with a gonadotrophin-releasing hormone analogue. J Urol 133: 612–614

    PubMed  Google Scholar 

  • Sundaram K, Connell KG, Bardin CW, Samojlik E, Schally AV (1982) Inhibition of pituitary-testicular function with (D-Trp6) luteinizing hormone-releasing hormone in rhesus monkeys. Endocrinology 110: 1308–1314

    Article  PubMed  CAS  Google Scholar 

  • Sundaram K, Thau R, Goldstein M, Philips DM, Rivier J, Bardin CW (1984 a) Effects of an LH-RH agonist on pituitary and testicular function in rhesus monkeys. J Reprod Fertil 72: 365–371

    Article  PubMed  CAS  Google Scholar 

  • Sundaram K, Schmidt F, Thau RB, Rivier J, Vale W, Bardin CW (1984b) Species differences in the sensitivity to the antitesticular effects of (Ac-D-Nal21,4FD-Phe2, D-Trp3, D-Arg6)-LH-RH, a potent LH-RH antagonist. Contraception 29: 271–281

    Article  PubMed  CAS  Google Scholar 

  • Suoranta H (1971) Changes in the small blood vessels of the adult human testis in relation to age and to some pathological conditions. Virchows Arch [A] 352: 165–181

    CAS  Google Scholar 

  • Tillinger KG (1957) Testicular morphology. Acta Endocrinol [Suppl] (Copenh) 30: 1–38

    Google Scholar 

  • Vicari E, Mongioi A, Recupero D, Coniglione F, Macclu M, Sipione C, Cologero A, D’Agata R (1986) Failure of GnRH analogue to inhibit serum concentrations of testosterone and 17 alpha-hydroxyprogesterone in hCG-substituted hypogonadotropic hypogonadism. Acta Endocrinol (Copenh) 113: 305–310

    CAS  Google Scholar 

  • Vickery BH (1985) Comparisons of the potential utility of LH-RH agonists and antagonists for fertility control. J Steroid Biochem 23: 779–791

    Article  PubMed  CAS  Google Scholar 

  • Vickery BH, McRae G (1980) Responses of the males of different laboratory species to continuous administration of an LH-RH agonist. J Androl 1: 62

    Google Scholar 

  • Vickery BH, McRae GI (1984) Male contraceptive potential of nafarelin acetate assessed in the dog. In: Vickery BH, Nestor JJ jr, Hafes ESE (eds) LH-RH and its analogs. MTP Press, Lancaster, pp 61–75

    Chapter  Google Scholar 

  • Vickery BH, McRae G, Bergström K, Biones W, Worden A, Seidenberg R (1983) Inability of continuous long-term administration of D-Nal (2)6-LH-RH to abolish fertility in male rats. J Androl 4: 283–291

    PubMed  CAS  Google Scholar 

  • Wang NG, Sundaram K, Pavlou S, Rivier J, Vale W, Bardin CW (1983) Mice are insensitive to the antitesticular effects of luteinizing hormone-releasing hormone agonists. Endocrinology 112: 331–335

    Article  PubMed  CAS  Google Scholar 

  • Waxman JH, Hendry WF, Whitfield HN, Wallace DMA, Oliver RTD (1984) Response and relapse in patients with prostatic cancer treated with buserelin. In: Labrie F, Belanger A, Dupont A (eds) LH-RH and its analogues. Amsterdam, Elsevier Science Publishers, pp 359–367

    Google Scholar 

  • Weinbauer GF, Nieschlag E (1985) Regulation of primate testicular function by GnRH analogues. Med Biol 63: 210–217

    CAS  Google Scholar 

  • Weinbauer GF, Surmann FJ, Akhtar FB, Shah GV, Vickery BH, Nieschlag E (1984) Reversible inhibition of testicular function by a gonadotropin hormone-releasing hormone antagonist in monkeys ( Macaca fascicularis ). Fertil Steril 42: 906–914

    PubMed  CAS  Google Scholar 

  • Weinbauer GF, Respondek M, Themann H, Nieschlag E (1987 a) Reversibility of long-term effects of GnRH agonist administration on testicular histology and sperm production in the non-human primate. J Androl 8: 319–329

    PubMed  CAS  Google Scholar 

  • Weinbauer GF, Arslan M, Khan SA, Nieschlag E (1987b) Androgens counteract the GnRH antagonist-induced suppression of FSH and spermatogenesis in rats. Acta Endocrinol (Copenh) 114: 186–187

    Google Scholar 

  • Weinbauer GF, Surmann FJ, Nieschlag E (1987c) Suppression of spermatogenesis in a nonhuman primate ( Macaca fascicularis) by concomitant gonadotropin-releasing hormone antagonist and testosterone treatment. Acta Endocrinol (Copenh) 114: 138–146

    CAS  Google Scholar 

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Weinbauer, G.F., Nieschlag, E. (1988). Reversibility of GnRH Agonist-Induced Inhibition of Testicular Function: Comparison Between Rat, Monkey and Man. In: Höffken, K. (eds) LH-RH Agonists in Oncology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73530-1_8

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