title: Cholinergic modulation of growth hormone responses to growth hormone-releasing hormone in uraemic patients on peritoneal dialysis.
abstract: BACKGROUND
  Hypothalamic cholinergic neurotransmission plays a major role in the regulation of GH secretion. Pyridostigmine, a cholinesterase inhibitor, is able to decrease hypothalamic somatostatinergic tone and release GH in normal subjects. Blockade of muscarinic receptor with pirenzepine blunts the GH release in several clinical situations. However, little information is available on the role played by central cholinergic pathways in GH regulation in uraemic patients.
  
  
  OBJECTIVE
  We aimed to assess GH responses to GHRH after pretreatment with pyridostigmine and pirenzepine in a group of uraemic patients undergoing peritoneal dialysis (PD). GH responses of the patients treated with recombinant human erythropeitin (rhEPO) were compared to patients without treatment.
  
  
  METHODS
  We studied 14 male patients on PD and nine control subjects. All subjects underwent three endocrine test in random order after an overnight fast. Each subject received GHRH (100 microg, i.v. in bolus at 0 minutes). Sixty minutes before the injection of GHRH subjects were given oral placebo, pyridostigmine (120 mg), or pirenzepine (100 mg).
  
  
  METHODS
  Blood samples for GH were collected at -60, 0, 15, 30, 45, 60 and 90 minutes The hormonal secretory responses were studied by a time-averaged (area under the curves, AUC) and time-independent (peak values) analysis.
  
  
  RESULTS
  Baseline GH concentrations were similar in patients and controls. GH responses to placebo plus GHRH were also comparable in patients and controls (peak 26.6 +/- 3.8 vs. 33.2 +/- 4.4 mU/l, AUC 28.2 +/- 3.4 vs. 27.8 +/- 4.6 mU/h/l). Pyridostigmine administration induced a significant potentiation of GH responses to GHRH both in patients (peak 43.2 +/- 5.2 mU/l, AUC 47.6 +/- 6.0 mU/h/l; P < 0.01) and in control subjects (peak 79.2 +/- 8.6 mU/l, AUC 78.0 +/- 9.4 mU/h/l; P < 0.01). However, the increment in GH peak and AUC was significantly (P < 0.05) greater in controls in relation to values found in patients. Pirenzepine administration induced an abolishment of GH release after GHRH stimulation both in PD patients (peak 5.4 +/- 2.6 mU/l, AUC 6.0 +/- 2.4 mU/h/l; P < 0.01) and in healthy controls (peak 3.8 +/- 0.6 mU/l, AUC 4.0 +/- 0.4 mU/h/l; P < 0.05). Responses to pyridostigmine plus GHRH and pirenzepine plus GHRH were similar in patients on chronic therapy with recombinant human erythropeitin and in patients without rhEPO therapy.
  
  
  CONCLUSIONS
  These results suggest that the cholinergic regulation of GH release is preserved in uraemic patients on peritoneal dialysis. The significantly lower increase in GH response to GHRH induced by pyridostigmine suggests that cholinergic stimulatory tone is attenuated in patients in relation to control subjects. Long-term therapy with rhEPO seems not to affect GH responses to cholinergic stimulation or blockade.
authors: Department of Endocrinology, Hospital La Paz, Madrid, Spain. mibarsd@infomed.es
authors: J J
authors: JJ
authors: Díez
authors: P
authors: P
authors: Iglesias
authors: R
authors: R
authors: Selgas
authors: M A
authors: MA
authors: Bajo
authors: A
authors: A
authors: Aguilera
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D004921:Erythropoietin / Q000627:therapeutic use; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000502:physiology*; D019382:Human Growth Hormone / Q000097:blood / Q000502:physiology*; D006801:Humans; D008297:Male; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D010530:Peritoneal Dialysis / Q000379:methods*; D010890:Pirenzepine / Q000627:therapeutic use; D011729:Pyridostigmine Bromide / Q000627:therapeutic use; D011994:Recombinant Proteins; D014511:Uremia / Q000503:physiopathology* / Q000628:therapy
chemical_list: D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D011994:Recombinant Proteins; D004921:Erythropoietin; D019382:Human Growth Hormone; D010890:Pirenzepine; D013007:Growth Hormone-Releasing Hormone; D011729:Pyridostigmine Bromide