title: The reduced release of GH by GHRH in 8 subjects aged 65-69 years is augmented considerably by rivastigmine, a drug for Alzheimer's disease.
abstract: BACKGROUND
  The growth hormone (GH) secretion declines by 14% with each decade of adult life. Several attempts have been made to reverse the manifestations of the senile GH deficiency, termed somatopause, but GH substitution treatment in old age has not yet developed an established regimen. Cholinesterase inhibitors like pyridostigmine are able to elicit GH secretion when administered alone and to enhance the GH response to growth hormone releasing hormone (GHRH), but its clinical use is limited due to the strong peripheral cholinergic side effects.
  
  
  OBJECTIVE
  The aims of our experiments were to find out whether the GH response to GHRH can be augmented by rivastigmine, a new orally applicable and well-tolerated selective inhibitor of cerebral acetylchoinesterase.
  
  
  METHODS
  Eight healthy volunteers (age range 65-69 years) were studied. After an overnight fast, GHRH tests were done: 1 microg/kg GHRH was injected as an intravenous bolus. Blood samples for an immunoradiometric GH assay were taken at the time of GHRH injection (time 0) and after 15, 30, 45, 60, and 120 min. First, the baseline experiment was done: it consisted of two subsequent GHRH tests which were carried out within an interval of 120 min. Four weeks later the rivastigmine experiment was done identically, but 60 min before performing the second GHRH test, rivastigmine (4.5 mg) was administered orally. The GH secretory responses were expressed as areas under the curve (AUC; median, interquartile range), Wilcoxon's signed-rank test was used for statistical comparisons.
  
  
  RESULTS
  Baseline experiment: The GH AUC of the first GHRH test was 1040 (range 420-1250) ng/ml/h. The repeated GHRH stimulation after 120 min (second GHRH test) showed a 13-fold decrease to 80 (range 60-130) ng/ml/h. Rivastigmine experiment: The GH AUC of the first GHRH test was 950 (range 540-1430) ng/ml/h and, therefore, similar to that of the baseline experiment. 60 min after ingestion of the single oral dose of rivastigmine (4.5 mg), the following GHRH stimulation (second GHRH test) nearly doubled the GH AUC to 1580 (range 860-3330) ng/ml/h. Comparing the DeltaGH AUC values (DeltaGH AUC = GH AUC of the first GHRH test minus GH AUC of the second GHRH test), baseline experiment versus rivastigmine experiment, there was a 20-fold (p = 0.018) increase in GH AUC after rivastigmine pretreatment.
  
  
  CONCLUSIONS
  Rivastigmine is a powerful drug to enhance GH release to repeated GHRH stimulation in healthy elderly human subjects. Future investigations are necessary to find out whether rivastigmine can restore the senile decline of the circadian GH secretion in the long term and, therefore, has new implications for patient treatment.
authors.affiliation: 1st Medical Department, Donauspital im Sozialmedizinischen Zentrum Ost der Stadt Wien, and Ludwig Boltzmann Institute for Aging Research, Vienna, Austria. rudolf.obermayr@chello.at
authors.forename: Rudolf P
authors.initials: RP
authors.lastname: Obermayr
authors.forename: Lothar
authors.initials: L
authors.lastname: Mayerhofer
authors.forename: Maarten
authors.initials: M
authors.lastname: Knechtelsdorfer
authors.forename: Karl H
authors.initials: KH
authors.lastname: Tragl
authors.forename: Georg
authors.initials: G
authors.lastname: Geyer
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy; D002219:Carbamates / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D005260:Female; D013006:Growth Hormone / Q000096:biosynthesis / Q000187:drug effects*; D013007:Growth Hormone-Releasing Hormone / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D048448:Phenylcarbamates; D000068836:Rivastigmine
chemical_list: D002219:Carbamates; D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D000068836:Rivastigmine