Disruption of the hypothalamic luteinizing hormone pulsing mechanism in aging men

Am J Physiol Regul Integr Comp Physiol. 2001 Dec;281(6):R1917-24. doi: 10.1152/ajpregu.2001.281.6.R1917.

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.

Publication types

  • 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.

MeSH terms

  • Adolescent
  • Adult
  • Aging / physiology*
  • Child
  • Child, Preschool
  • Entropy
  • Gonadotropin-Releasing Hormone / metabolism
  • Humans
  • Hypothalamus / growth & development*
  • Kinetics
  • Luteinizing Hormone / metabolism*
  • Male
  • Models, Biological
  • Reference Values
  • Signal Transduction / physiology

Substances

  • Gonadotropin-Releasing Hormone
  • Luteinizing Hormone