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.
Keenan
Daniel M
DM
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.
Veldhuis
Johannes D
JD
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