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. 1988 Apr;81(4):1020–1029. doi: 10.1172/JCI113412

Attenuated release of biologically active luteinizing hormone in healthy aging men.

R J Urban 1, J D Veldhuis 1, R M Blizzard 1, M L Dufau 1
PMCID: PMC329626  PMID: 3280599

Abstract

To examine the biological quality and physiologically pulsatile mode of endogenous luteinizing hormone release in active, healthy aging men, we used the rat interstitial-cell testosterone in vitro bioassay to probe LH bioactivity in response to (a) endogenous gonadotropin-releasing hormone (GnRH) action (basal pulsatile bioactive LH secretion); (b) exogenous GnRH stimulation (10 micrograms IV pulses); and (c) inhibition of endogenous estrogen negative feedback (treatment with a nonsteroidal antiestrogen, tamoxifen). Basally, some healthy older men exhibited evidence of neuroendocrine dysfunction, reflected by irregular bursts of bioactive LH release followed by transiently low plasma bio:immuno (B:I) LH ratios. However, mean basal plasma bioactive LH concentrations, B:I ratios, and spontaneous LH pulse properties (peak frequency, amplitude, duration, and enhanced B:I ratios within LH peaks) were not altered in older men. On the other hand, augmentation of bioactive LH secretion and enhancement of plasma B:I ratios by pulsed injections of exogenous GnRH were either significantly reduced or absent in older men. In addition, although tamoxifen increased bioactive LH pulse frequency in both age groups and facilitated exogenous GnRH action in some subjects, older men increased their 12-h mean bioactive LH concentrations, B:I ratios, and bioactive LH peak amplitudes to a significantly lesser degree than young men. In summary, young and older healthy men exhibit similar mean basal plasma bioactive LH concentrations and spontaneous LH pulse properties. However, pituitary bioactive LH reserve is markedly attenuated in older men challenged with either exogenous GnRH or antiestrogen. Accordingly, we conclude that healthy aging men manifest an impaired secretory reserve for biologically active LH release.

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Selected References

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  1. Baker H. W., Burger H. G., de Kretser D. M., Hudson B., O'Connor S., Wang C., Mirovics A., Court J., Dunlop M., Rennie G. C. Changes in the pituitary-testicular system with age. Clin Endocrinol (Oxf) 1976 Jul;5(4):349–372. doi: 10.1111/j.1365-2265.1976.tb01964.x. [DOI] [PubMed] [Google Scholar]
  2. Beitins I. Z., Dufau M. L., O'Loughlin K., Catt K. J., McArthur J. W. Analysis of biological and immunological activities in the two pools of LH released during constant infusion of luteinizing hormone-releasing hormone (LHRH) in men. J Clin Endocrinol Metab. 1977 Sep;45(3):605–608. doi: 10.1210/jcem-45-3-605. [DOI] [PubMed] [Google Scholar]
  3. Buckingham J. C., Wilson C. A. Peripubertal changes in the nature of LH. J Endocrinol. 1985 Feb;104(2):173–177. doi: 10.1677/joe.0.1040173. [DOI] [PubMed] [Google Scholar]
  4. Celani M. F., Montanini V., Baraghini G. F., Carani C., Marrama P. Effects of acute stimulation with gonadotropin releasing hormone (GnRH) on biologically active serum luteinizing hormone (LH) in elderly men. J Endocrinol Invest. 1984 Dec;7(6):589–595. doi: 10.1007/BF03349491. [DOI] [PubMed] [Google Scholar]
  5. Davidson J. M., Chen J. J., Crapo L., Gray G. D., Greenleaf W. J., Catania J. A. Hormonal changes and sexual function in aging men. J Clin Endocrinol Metab. 1983 Jul;57(1):71–77. doi: 10.1210/jcem-57-1-71. [DOI] [PubMed] [Google Scholar]
  6. Deslypere J. P., Kaufman J. M., Vermeulen T., Vogelaers D., Vandalem J. L., Vermeulen A. Influence of age on pulsatile luteinizing hormone release and responsiveness of the gonadotrophs to sex hormone feedback in men. J Clin Endocrinol Metab. 1987 Jan;64(1):68–73. doi: 10.1210/jcem-64-1-68. [DOI] [PubMed] [Google Scholar]
  7. Dufau M. L., Beitins I. Z., McArthur J. W., Catt K. J. Effects of luteinizing hormone releasing hormone (LHRH) upon bioactive and immunoreactive serum LH levels in normal subjects. J Clin Endocrinol Metab. 1976 Sep;43(3):658–667. doi: 10.1210/jcem-43-3-658. [DOI] [PubMed] [Google Scholar]
  8. Dufau M. L., Hodgen G. D., Goodman A. L., Catt K. J. Bioassay of circulating luteinizing hormone in the rhesus monkey: comparison with radioimmunoassay during physiological changes. Endocrinology. 1977 Jun;100(6):1557–1565. doi: 10.1210/endo-100-6-1557. [DOI] [PubMed] [Google Scholar]
  9. Dufau M. L., Pock R., Neubauer A., Catt K. J. In vitro bioassay of LH in human serum: the rat interstitial cell testosterone (RICT) assay. J Clin Endocrinol Metab. 1976 May;42(5):958–969. doi: 10.1210/jcem-42-5-958. [DOI] [PubMed] [Google Scholar]
  10. Dufau M. L., Veldhuis J. D., Fraioli F., Johnson M. L., Beitins I. Z. Mode of secretion of bioactive luteinizing hormone in man. J Clin Endocrinol Metab. 1983 Nov;57(5):993–1000. doi: 10.1210/jcem-57-5-993. [DOI] [PubMed] [Google Scholar]
  11. Dufau M. L., Veldhuis J. D. Pathophysiological relationships between the biological and immunological activities of luteinizing hormone. Baillieres Clin Endocrinol Metab. 1987 Feb;1(1):153–176. doi: 10.1016/s0950-351x(87)80057-5. [DOI] [PubMed] [Google Scholar]
  12. Harman S. M., Tsitouras P. D., Costa P. T., Blackman M. R. Reproductive hormones in aging men. II. Basal pituitary gonadotropins and gonadotropin responses to luteinizing hormone-releasing hormone. J Clin Endocrinol Metab. 1982 Mar;54(3):547–551. doi: 10.1210/jcem-54-3-547. [DOI] [PubMed] [Google Scholar]
  13. Karpas A. E., Bremner W. J., Clifton D. K., Steiner R. A., Dorsa D. M. Diminished luteinizing hormone pulse frequency and amplitude with aging in the male rat. Endocrinology. 1983 Mar;112(3):788–792. doi: 10.1210/endo-112-3-788. [DOI] [PubMed] [Google Scholar]
  14. Karpas A. E., Matsumoto A. M., Paulsen C. A., Bremner W. J. Elevated serum follicle-stimulating hormone levels in men with normal seminal fluid analyses. Fertil Steril. 1983 Mar;39(3):333–336. doi: 10.1016/s0015-0282(16)46881-0. [DOI] [PubMed] [Google Scholar]
  15. Meites J., Steger R. W., Huang H. H. Relation of neuroendocrine system to the reproductive decline in aging rats and human subjects. Fed Proc. 1980 Dec;39(14):3168–3172. [PubMed] [Google Scholar]
  16. Moroz E. V., Verkhratsky N. S. Hypophyseal-gonadal system during male aging. Arch Gerontol Geriatr. 1985 Apr;4(1):13–19. doi: 10.1016/0167-4943(85)90013-5. [DOI] [PubMed] [Google Scholar]
  17. Steiner R. A., Bremner W. J., Clifton D. K., Dorsa D. M. Reduced pulsatile luteinizing hormone and testosterone secretion with aging in the male rat. Biol Reprod. 1984 Sep;31(2):251–258. doi: 10.1095/biolreprod31.2.251. [DOI] [PubMed] [Google Scholar]
  18. Veldhuis J. D., Beitins I. Z., Johnson M. L., Serabian M. A., Dufau M. L. Biologically active luteinizing hormone is secreted in episodic pulsations that vary in relation to stage of the menstrual cycle. J Clin Endocrinol Metab. 1984 Jun;58(6):1050–1058. doi: 10.1210/jcem-58-6-1050. [DOI] [PubMed] [Google Scholar]
  19. Veldhuis J. D., Carlson M. L., Johnson M. L. The pituitary gland secretes in bursts: appraising the nature of glandular secretory impulses by simultaneous multiple-parameter deconvolution of plasma hormone concentrations. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7686–7690. doi: 10.1073/pnas.84.21.7686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Veldhuis J. D., Dufau M. L. Estradiol modulates the pulsatile secretion of biologically active luteinizing hormone in man. J Clin Invest. 1987 Sep;80(3):631–638. doi: 10.1172/JCI113115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Veldhuis J. D., Fraioli F., Rogol A. D., Dufau M. L. Metabolic clearance of biologically active luteinizing hormone in man. J Clin Invest. 1986 Apr;77(4):1122–1128. doi: 10.1172/JCI112411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Veldhuis J. D., Johnson M. L. Cluster analysis: a simple, versatile, and robust algorithm for endocrine pulse detection. Am J Physiol. 1986 Apr;250(4 Pt 1):E486–E493. doi: 10.1152/ajpendo.1986.250.4.E486. [DOI] [PubMed] [Google Scholar]
  23. Veldhuis J. D., Johnson M. L., Dufau M. L. Preferential release of bioactive luteinizing hormone in response to endogenous and low dose exogenous gonadotropin-releasing hormone pulses in man. J Clin Endocrinol Metab. 1987 Jun;64(6):1275–1282. doi: 10.1210/jcem-64-6-1275. [DOI] [PubMed] [Google Scholar]
  24. Veldhuis J. D., Rogol A. D., Johnson M. L. Endogenous opiates modulate the pulsatile secretion of biologically active luteinizing hormone in man. J Clin Invest. 1983 Dec;72(6):2031–2040. doi: 10.1172/JCI111168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Veldhuis J. D., Sowers J. R., Rogol A. D., Klein F. A., Miller N., Dufau M. L. Pathophysiology of male hypogonadism associated with endogenous hyperestrogenism. Evidence for dual defects in the gonadal axis. N Engl J Med. 1985 May 23;312(21):1371–1375. doi: 10.1056/NEJM198505233122107. [DOI] [PubMed] [Google Scholar]
  26. Warner B. A., Dufau M. L., Santen R. J. Effects of aging and illness on the pituitary testicular axis in men: qualitative as well as quantitative changes in luteinizing hormone. J Clin Endocrinol Metab. 1985 Feb;60(2):263–268. doi: 10.1210/jcem-60-2-263. [DOI] [PubMed] [Google Scholar]
  27. Warner B., Worgul T. J., Drago J., Demers L., Dufau M., Max D., Santen R. J. Effect of very high dose D-leucine6-gonadotropin-releasing hormone proethylamide on the hypothalamic-pituitary testicular axis in patients with prostatic cancer. J Clin Invest. 1983 Jun;71(6):1842–1853. doi: 10.1172/JCI110940. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Zanisi M., Messi E., Martini L. In vitro release of luteinizing hormone-releasing hormone from the hypothalamus of old male rats. Endocrinology. 1987 Jan;120(1):49–54. doi: 10.1210/endo-120-1-49. [DOI] [PubMed] [Google Scholar]
  29. Zumoff B., Strain G. W., Kream J., O'Connor J., Rosenfeld R. S., Levin J., Fukushima D. K. Age variation of the 24-hour mean plasma concentrations of androgens, estrogens, and gonadotropins in normal adult men. J Clin Endocrinol Metab. 1982 Mar;54(3):534–538. doi: 10.1210/jcem-54-3-534. [DOI] [PubMed] [Google Scholar]

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