title: Age attenuates testosterone secretion driven by amplitude-varying pulses of recombinant human luteinizing hormone during acute gonadotrope inhibition in healthy men.
abstract: BACKGROUND
  Whether testosterone (Te) depletion in aging men reflects deficits in the testis, hypothalamus, and/or pituitary gland is unknown.
  
  
  OBJECTIVE
  Our objective was to quantify the impact of age on gonadal Te secretion driven by amplitude-varying pulses of recombinant human LH (rhLH) in the absence of confounding by endogenous hypothalamo-pituitary signals.
  
  
  METHODS
  This was a double-blind, placebo-controlled study.
  
  
  METHODS
  The setting was an academic medical center.
  
  
  METHODS
  Fifteen healthy community-dwelling men ages 22-78 yr were included in the study.
  
  
  METHODS
  Saline or four separate rhLH doses were each infused twice iv in randomized order as one pulse every 2 h over 20 h to stimulate Te secretion, after LH secretion was suppressed by a GnRH-receptor antagonist, ganirelix.
  
  
  RESULTS
  LH and Te concentrations were determined in blood samples collected every 5 min. Maximal and minimal (as well as mean) Te responses were regressed linearly on age to reflect LH peak and nadir (and average) effects, respectively.
  
  
  RESULTS
  The ganirelix/rhLH paradigm yielded serum LH concentrations of 4.6 +/- 0.22 IU/liter (normal range 1-9). By regression analysis, age was associated with declines in rhLH pulse-stimulated peak and nadir (and mean) concentrations of total Te (P = 0.0068), bioavailable Te (P = 0.0096), and free Te (P = 0.013), as well as lower Te/LH concentration ratios (P < 0.005). Deconvolution analysis suggested that the half-life of infused LH increases by 12%/decade (P = 0.044; R(2) = 0.28).
  
  
  CONCLUSIONS
  Infusion of amplitude-varying pulses of rhLH during gonadal-axis suppression in healthy men unmasks prominent age-related deficits in stimulated total (39%), bioavailable (66%), and free (63%) Te concentrations, and a smaller age-associated increase in LH half-life. These data suggest that age-associated factors reduce the efficacy of LH pulses.
authors.affiliation: Endocrine Research Unit, Department of Internal Medicine, General Clinical Research Center, Mayo Medical and Graduate Schools of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Paul Y
authors.initials: PY
authors.lastname: Takahashi
authors.forename: Patrick
authors.initials: P
authors.lastname: Votruba
authors.forename: Mohammed
authors.initials: M
authors.lastname: Abu-Rub
authors.forename: Kristi
authors.initials: K
authors.lastname: Mielke
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007986:Luteinizing Hormone / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011673:Pulsatile Flow; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000008:administration & dosage; D013739:Testosterone / Q000097:blood / Q000378:metabolism*
chemical_list: D010919:Placebos; D011966:Receptors, LHRH; D011994:Recombinant Proteins; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; C061018:ganirelix