Disruption of the hypothalamic luteinizing hormone pulsing mechanism in aging men.

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  • Author(s): Keenan DM;Keenan DM; Veldhuis JD
  • Source:
    American journal of physiology. Regulatory, integrative and comparative physiology [Am J Physiol Regul Integr Comp Physiol] 2001 Dec; Vol. 281 (6), pp. R1917-24.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901230 Publication Model: Print Cited Medium: Print ISSN: 0363-6119 (Print) Linking ISSN: 03636119 NLM ISO Abbreviation: Am J Physiol Regul Integr Comp Physiol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Bethesda, Md. : American Physiological Society
    • Subject Terms:
      Aging/*physiology ; Hypothalamus/*growth & development ; Luteinizing Hormone/*metabolism; Adolescent ; Adult ; Child ; Child, Preschool ; Entropy ; Gonadotropin-Releasing Hormone/metabolism ; Humans ; Kinetics ; Male ; Models, Biological ; Reference Values ; Signal Transduction/physiology
    • Abstract:
      The incremental nature of neuroendocrine aging suggests that subtle system dysregulation may precede overt axis failure. The present analyses unmask threefold disruption of pulsatile gonadotropin-releasing hormone (GnRH)-luteinizing hormone (LH) secretion in the aging male. First, by way of random effects-based deconvolution analysis, we document an elevated daily GnRH-LH pulse frequency in healthy older men [namely, mean (+/-SE) 23 +/- 1 (older) vs. 15 +/- 1 (young) LH secretory bursts/24 h, P < 0.001] and lower mean LH pulse mass [3.73 +/- 0.58 (older) vs. 5.46 +/- 0.66 (young) IU/l, P = 0.038]. However, total LH secretion rates and two-compartment LH elimination kinetics were comparable in the two age cohorts. Second, using the approximate entropy statistic, we show an equivalently random order-dependent succession of LH interpulse-interval lengths in young and older men, but a marked age-related deterioration of the ad seriatim regularity of LH pulse mass series in older individuals (P = 0.0057). Third, by modeling GnRH pulse-generator output as a Weibull renewal process (generalized Gamma density) to emulate loosely coupled GnRH neuronal oscillators, we identify an age-related reduction in the frequency-independent and order-independent variability of GnRH-LH interpulse-interval sets (P = 0.08). These findings indicate that the GnRH-LH pulsing mechanism in healthy older men maintains an increased mean frequency and lower amplitude of bursting activity, a reduced uniformity of serial LH pulse-mass values, and an impaired variability among interpulse-interval lengths. Thereby, the foregoing order-dependent and order-independent alterations in GnRH-LH signal generation in the aging human suggest a general framework for exploring subtle disruption of time-sensitive regulation of other neurointegrative systems.
    • Grant Information:
      M01-RR-00847 United States RR NCRR NIH HHS; U54-HD-28934 United States HD NICHD NIH HHS
    • Accession Number:
      33515-09-2 (Gonadotropin-Releasing Hormone)
      9002-67-9 (Luteinizing Hormone)
    • Publication Date:
      Date Created: 20011114 Date Completed: 20020102 Latest Revision: 20200930
    • Publication Date:
      20231215
    • Accession Number:
      10.1152/ajpregu.2001.281.6.R1917
    • Accession Number:
      11705778