Disappearance of endogenous luteinizing hormone is prolonged in postmenopausal women (original) (raw)

Abstract

Pituitary secretion of LH is increased after menopause, but it is not known whether changes in LH clearance also contribute to elevated serum levels. To determine whether the disappearance of endogenous LH is decreased in postmenopausal women (PMW), compared with normal cycling women, GnRH receptor blockade was used to inhibit endogenous secretion of LH and the glycoprotein free alpha-subunit (FAS), and the decline of serum levels was monitored. The NAL-GLU GnRH antagonist ([Ac-D-2Nal1,D-4ClPhe2, D-3Pal3,Arg5,D-4-p-methoxybenzoyl-2-aminobutyric acid6,D-Ala10]GnRH) was administered s.c., at doses of 5, 15, 50, and 150 microg/kg, to 15 euthyroid PMW in 21 studies. Blood was sampled every 10 min, for 4 h before and 8 h after a single sc injection of the GnRH antagonist, followed by hourly samples, ending at 20 h after injection. Results of the maximally suppressive doses (50 and 150 microg/kg) were compared with those of 24 normal cycling women in the early follicular phase and late fo...

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References (43)

  1. Gharib SD, Wierman ME, Shupnik MA, Chin WW. 1990 Molecular biology of the pituitary gonadotropins. Endocr Rev. 11:177-199.
  2. Kohler PO, Ross GT, ODell WD. 1968 Metabolic clearance and production rates of human luteinizing hormone in pre-and postmenopausal women. J Clin Invest. 47:38 -47.
  3. Siler TM, Yen SSC. 1973 Augmented gonadotropin response to synthetic LRF in hypogonadal state. J Clin Endocrinol Metab. 37:491-494.
  4. Pepperell RJ, De Kretser DM, Burger HG. 1975 Studies on the metabolic clearance rate and production rate of human luteinizing hormone and on the initial half-time of its subunits in man. J Clin Invest. 56:118 -126.
  5. Wide L. 1985 Median charge and charge heterogeneity of human pituitary FSH, LH, and TSH. Acta Endocrinol (Copenh). 109:190 -197.
  6. Snyder PJ, Bashey HM, Montecinos A, ODell WD, Spratt DI. 1989 Secretion of multiple forms of human luteinizing hormone by cultured fetal human pituitary cells. J Clin Endocrinol Metab. 68:1033-1038.
  7. Wilson CA, Leigh AJ, Chapman AJ. 1989 Gonadotrophin glycosylation and function. J Endocrinol. 125:3-14.
  8. Thotakura NR, Blithe DL. 1995 Glycoprotein hormones: glycobiology of go- nadotrophins, thyrotrophin and free ␣-subunit. Glycobiology. 5:3-10.
  9. Ulloa-Aguirre A, Midgley Jr AR, Beitins IZ, Padmanabhan V. 1995 Follicle- stimulating isohormones: characterization and physiological relevance. En- docr Rev. 16:765-787.
  10. Weick RF. 1977 A comparison of the disappearance rates of luteinizing hor- mone from intact and ovariectomized rats. Endocrinology. 101:157-161.
  11. Yen SSC, Llerena LA, Little B, Pearson OH. 1968 Disappearance rates of endogenous luteinizing hormone and chorionic gonadotropin in man. J Clin Endocrinol Metab. 28:1763-1767.
  12. Booth RA, Weltman JY, Yankov VI, et al. 1996 Mode of pulsatile follicle- stimulating hormone secretion in gonadal hormone-sufficient and -deficient women-a clinical research center study. J Clin Endocrinol Metab. 81:3208 -3214.
  13. Hall JE, Taylor AE, Martin KA, Rivier JE, Schoenfield DA, Crowley Jr FW. 1994 Decreased release of gonadotropin-releasing hormone (GnRH) during the preovulatory, midcycle luteinizing hormone (LH) surge in normal women. Proc Natl Acad Sci USA. 91:6894 -6898.
  14. Filicori M, Butler JP, Crowley Jr WF. 1984 Neuroendocrine regulation of the corpus luteum in the human. Evidence for pulsatile progesterone secretion. J Clin Invest. 73:1638 -1647.
  15. Whitcomb RW, Sangha JS, Schneyer AL, Crowley Jr WF. 1988 Improved measurement of free alpha subunit of glycoprotein hormones by assay with use of a monoclonal antibody. Clin Chem. 34:2022-2025.
  16. Crowley Jr WF, Beitins IZ, Vale WW, et al. 1980 The biologic activity of a potent analogue of gonadotropin releasing hormone in normal and hypogo- nadotropic men. N Engl J Med. 302:1052-1057.
  17. Gabrielsson J, Weiner D. 1994 Pharmacokinetic and pharmacodynamic data analysis. 34 -40-107-114. Stockholm, Sweden: Swedish Pharmaceutical Press.
  18. Lam FC, Hung CT, Perrier DG. 1985 Estimation of variance for harmonic mean half-lives. J Pharm Sci. 74:229 -231.
  19. Nakamura Y, Nomura K, Watanabe M, Ujihara M, Demura H. 1993 Com- parison of biological aspects among ovine luteinizing hormone isoforms with charge heterogeneity. Endocr J. 40:73-81.
  20. Burgon PG, Stanton PG, Robertson DM. 1996 In vivo bioactivities and clear- ance patterns of highly purified human luteinizing hormone isoforms. Endo- crinology. 137:4827-4836.
  21. Baenziger JU, Kumar S, Brodbeck RM, Smith PL, Beranek MC. 1992 Cir- culatory half-life but not interaction with the lutropin/chorionic gonadotropin receptor is modulated by sulfation of bovine lutropin oligosaccharides. Proc Natl Acad Sci USA. 89:334 -338.
  22. Raiti S, Maclaren NK, Akesode FA. 1980 Precocious and delayed puberty. Studies of FSH and LH production and metabolism. Acta Endocrinol (Copenh). 94:475-479.
  23. Mortola JF, Hsueh AJW, Sathanandan M, et al. 1989 Suppression of bioactive and immunoreactive follicle-stimulating hormone and luteinizing hormone levels by a potent gonadotropin-releasing hormone antagonist: pharmacody- namic studies. Fertil Steril. 51:957-963.
  24. Urban RJ, Pavlou SN, Rivier JE, Vale WW, Dufau ML, Veldhuis JD. 1990 Suppressive actions of a gonadotropin-releasing hormone antagonist on lu- teinizing hormone, follicle-stimulating hormone, and prolactin release in es- trogen-deficient postmenopausal women. Am J Obstet Gynecol. 162:1225-1260.
  25. Couzinet B, Lahlou N, Thomas G, et al. 1991 Effects of gonadotrophin re- leasing hormone antagonist and agonist on the pulsatile release of gonado- trophins and ␣-subunit in postmenopausal women. Clin Endocrinol (Oxf). 34:477-483.
  26. Matikainen T, Ying-Qing D, Vergara M, Huhtaniemi I, Couzinet B, Schaison G. 1992 Differing responses of plasma bioactive and immunoreactive follicle- stimulating hormone and luteinizing hormone to gonadotropin-releasing hor- mone antagonist and agonist treatments in postmenopausal women. J Clin Endocrinol Metab. 75:820 -825.
  27. Karten MJ, Rivier JE. 1986 Gonadotropin-releasing hormone analog design. Structure-function studies toward the development of agonists and antago- nists: rationale and perspective. Endocr Rev. 7:44 -66.
  28. Winters SJ, Troen P. 1985 Pulsatile secretion of immunoreactive alpha-subunit secretion in man. J Clin Endocrinol Metab. 60:344 -348.
  29. Crowley Jr WF, Taylor AE, Martin KA, Whitcomb RW, Finkelstein JS, Hall JE. 1994 Use of the free alpha subunit (FAS) of glycoprotein secreting hormones as a surrogate marker of GnRH secretion in the human. Lusbader JW, Puett JD, Ruddon R, eds. Glycoprotein hormones: structure, function and clinical implications. Serono Symposia, , 1994, pp 253-263.
  30. Wang CF, Lasley BL, Lein A, Yen SSC. 1976 The functional changes of the pituitary gonadotrophs during the menstrual cycle. J Clin Endocrinol Metab. 42:718 -728.
  31. Urban RJ, Veldhuis JD, Dufau ML. 1991 Estrogen regulates the gonadotropin- releasing hormone-stimulated secretion of biologically active luteinizing hor- mone. J Clin Endocrinol Metab. 72:660 -668.
  32. Veldhuis JD, Fraioli F, Rogol AD, Dufau ML. 1986 Metabolic clearance of biologically active luteinizing hormone in man. J Clin Invest. 77:1122-1128.
  33. Whitcomb RW, O'Dea LStL, Finkelstein JS, Heavern D, Crowley Jr WF. 1990 Utility of free ␣-subunit as an alternative neuroendocrine marker of gonado- tropin-releasing hormone (GnRH) stimulation of the gonadotroph in the hu- man: evidence from normal and GnRH-deficient men. J Clin Endocrinol Metab. 70:1654 -1661.
  34. Kourides IA, Re RN, Weintraub BD, Ridgway EC, Maloof F. 1977 Metabolic clearance and secretion rates of subunits of human thyrotropin. J Clin Invest. 59:508 -516.
  35. le Cotonnec J-Y, Porchet HC, Beltrami V, Munafo A. 1998 Clinical pharma- cology of recombinant human luteinizing hormone: part 1. Pharmacokinetics after intravenous administration to healthy female volunteers and comparison with urinary human luteinizing hormone. Fertil Steril. 69:189 -194.
  36. Emmanouel DS, Stavropoulos T, Katz AI. 1994 Role of the kidney in me- tabolism of gonadotropins in rats. Am J Physiol. 247:E786 -E792.
  37. Bishop LA, Nguyen TV, Schofield PR. 1995 Both of the ␤-subunit carbohy- drate residues of follicle-stimulating hormone determine the metabolic clear- ance rate and in vivo potency. Endocrinology. 136:2635-2640.
  38. Fiete D, Srivastava V, Hindsgaul O, Baenziger JU. 1991 A hepatic reticu- loendothelial cell receptor specific for SO 4 -4GalNAc␤1,4GlcNAc␤1,2 Man␣ that mediates rapid clearance of lutropin. Cell. 67:1103-1110.
  39. Green ED, Baenziger JU. 1988 Asparagine-linked oligosaccharides on lutropin, follitropin, and thyrotropin. J Biol Chem. 263:36 -44.
  40. Wehmann RE, Nixon WE. 1979 Metabolic clearance rates of the subunits of human chorionic gonadotropin in man. J Clin Endocrinol Metab. 48:753-759.
  41. Zwart AD, Urban RJ, ODell WD, Veldhuis JD. 1996 Contrasts in the gona- dotropin-releasing hormone dose-response relationships for luteinizing hor- mone, follicle-stimulating hormone and ␣-subunit release in young vs. older men: appraisal with high-specificity immunoradiometric assay and deconvo- lution analysis. Eur J Endocrinol. 135:399 -406.
  42. Bone and Tooth Society Meeting June 22-24, 1999
  43. Bristol, United Kingdom Organizers: John Beresford (Bath) and Jon Tobias (Bristol). Abstract deadline is March 1, 1999. Further details available from Janet Crompton, 29 North Road, St. Andrews, Bristol BS6 5AD, United Kingdom. Telephone: ϩ44-117-924-8160; fax: ϩ44-117-924-1208; E-mail: janetcrompton@compuserve.com