Divergent gonadotropin-gonadal dose-responsive coupling in healthy young and aging men

Daniel M. Keenan, Johannes D. Veldhuis

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


The present study extends a recent composite model of in vivo interglandular signaling to assess the impact of age on 1) nonequilibrium exchange among diffusible and protein-bound testosterone (Te); 2) elimination of total and free Te; 3) basal and pulsatile Te secretion (sec); 4) the implicit feedforward function mediating luteinizing hormone (LH) concentration (con) drive of instantaneous Te sec; and 5) possible stochastic variability of the predicted LH con-Te sec dose-response linkage. To this end, we measured LH and Te con every 10 min for 24 h in healthy young (n = 13) and older men (n = 13). Statistical comparisons of analytic estimates revealed that elderly subjects manifest 1) reduced maximal burstlike LH-stimulated Te sec (impaired stimulus efficacy); 2) depressed half-maximally LH-stimulated Te sec (lower Leydig-cell responsivity); 3) decreased pulsatile and total Te sec; 4) elevated basal Te sec; 5) a prolonged half-life of total but not free Te con; and 6) delayed time evolution of LH and Te sec bursts. In contradistinction, age did not influence estimated LH-pulse potency (ED50), steroidogenic sensitivity (slope term), or stochastic variability of LH-Te coupling. On the basis of these data, we postulate that aging in the human male alters specific dose-response attributes linking LH con and Te sec and disrupts the time waveform of LH and Te sec bursts.

Original languageEnglish (US)
Pages (from-to)R381-R389
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number2 55-2
StatePublished - Feb 2004


  • Androgen
  • Feedforward
  • Human
  • Leydig feedback
  • Luteinizing hormone linkage
  • Male
  • Reproduction
  • Testis
  • Testosterone

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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