TY - JOUR
T1 - Disruption of the hypothalamic luteinizing hormone pulsing mechanism in aging men
AU - Keenan, Daniel M.
AU - Veldhuis, Johannes D.
PY - 2001
Y1 - 2001
N2 - 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/1, 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 pulsemass 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.
AB - 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/1, 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 pulsemass 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.
KW - Age
KW - Androgen
KW - Human
KW - Hypothalamus
KW - Male
KW - Pituitary
KW - Reproduction
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U2 - 10.1152/ajpregu.2001.281.6.r1917
DO - 10.1152/ajpregu.2001.281.6.r1917
M3 - Article
C2 - 11705778
AN - SCOPUS:0035665125
SN - 0363-6119
VL - 281
SP - R1917-R1924
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 6 50-6
ER -