Divergent gonadotropin-gonadal dose-responsive coupling in healthy young and aging men.
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.
Division of Endocrinology and Metabolism, Dept. of Internal Medicine, Mayo Medical and Graduate Schools of Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.
Daniel M
DM
Keenan
Johannes D
JD
Veldhuis
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005246:Feedback; D006207:Half-Life; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011673:Pulsatile Flow; D013269:Stochastic Processes; D013739:Testosterone / Q000737:chemistry / Q000378:metabolism*
D013739:Testosterone; D007986:Luteinizing Hormone