title: Dopaminergic and cholinergic involvement in the inhibitory effect of dexamethasone on the TSH response to TRH.
abstract: BACKGROUND
  Glucocorticoid administration is associated with reduced basal thyroid-stimulating hormone (TSH) levels and a blunted TSH response to thyrotropin-releasing hormone (TRH), despite thyroid hormone levels within the normal range. In light of the inhibitory effect of somatostatin and dopamine on TSH secretion, we examined whether this condition is caused by glucocorticoids through an increased hypothalamic somatostatinergic and/or dopaminergic inhibitory control of TSH. We measured the TSH response to TRH and serum-free T4 and T3 levels. The study group comprised 18 normal men (age 24-35) within 10% of the ideal body weight, randomly divided into 3 groups of six.
  
  
  METHODS
  We used the antidopaminergic agent metoclopramide (MCP) and the acetylcholinesterase inhibitor pyridostigmine, which enhances acetylcholine and thus inhibits hypothalamic somatostatin release. Subjects from group 1 were tested with TRH (20 micrograms in an intravenous bolus) after placebo, dexamethasone (dex) (2 mg/day in 4 divided doses for 3 days before the experimental day), or dex plus pyridostigmine (120 mg p.o.). Subjects from group 2 were tested with TRH after placebo, dex, or dex plus MCP (2.5 mg in an i.v. bolus injection). Subjects from group 3 were tested with TRH after placebo, dex, or dex plus pyridostigmine plus MCP.
  
  
  RESULTS
  In all subjects from groups 1, 2, and 3, TRH-induced TSH rise was significantly lower after dex than after placebo treatment. Neither pyridostigmine nor MCP, given alone, changed the TSH response to TRH after dex treatment. In contrast, the concomitant administration of MCP and pyridostigmine significantly enhanced the TRH-induced TSH rise in dex-treated subjects and made the TSH response to TRH similar to that observed in the TRH plus placebo test.
  
  
  CONCLUSIONS
  These data indicate that enhanced-hypothalamic somatostatinergic and dopaminergic inhibitory activities are involved in the mechanism underlying the reduced TSH response to TRH induced by glucocorticoid treatment.
authors.affiliation: Department of Internal Medicine and Biomedical Sciences, University of Parma, Italy. volpi@ipruniv.cce.unipr.it
authors.forename: V
authors.initials: V
authors.lastname: Coiro
authors.forename: R
authors.initials: R
authors.lastname: Volpi
authors.forename: S
authors.initials: S
authors.lastname: Cataldo
authors.forename: L
authors.initials: L
authors.lastname: Capretti
authors.forename: G
authors.initials: G
authors.lastname: Caffarri
authors.forename: S
authors.initials: S
authors.lastname: Pilla
authors.forename: P
authors.initials: P
authors.lastname: Chiodera
mesh_terms: D000328:Adult; D002794:Choline / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D011729:Pyridostigmine Bromide / Q000494:pharmacology; D013972:Thyrotropin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D018492:Dopamine Antagonists; D005938:Glucocorticoids; D013973:Thyrotropin-Releasing Hormone; D003907:Dexamethasone; D013972:Thyrotropin; D011729:Pyridostigmine Bromide; D008787:Metoclopramide; D002794:Choline; D004298:Dopamine