title: Dose-response studies with protirelin.
abstract: BACKGROUND
  A reduced thyrotropin (TSH) response to thyrotropin-releasing hormone (protirelin [TRH]) has been found consistently in a portion of patients with major depression. One hypothesis to explain this observation is that pituitary TRH receptors are down-regulated in major depression. One prediction stemming from this hypothesis is that prolactin (PRL) as well as TSH responses to TRH should be attenuated. To adequately test the pattern of protirelin-induced TSH and PRL responses with a protirelin dose-response design is necessary.
  
  
  METHODS
  Four doses of protirelin (25, 100, 500, and 800 micrograms) were infused in an ascending schedule at intervals of 3 to 7 days in patients with major depression and in control subjects. Seven women and six men with major depression were compared with age- and gender-matched controls (five women and seven men). The TSH and PRL responses were measured at regular intervals following each dose of protirelin.
  
  
  RESULTS
  No significant group differences in baseline levels of thyroid hormones or cortisol were present. Depressed men exhibited significant reductions in both TSH and PRL responses to protirelin across all doses compared with control men. Depressed women exhibited significant reductions in TSH responses but not in PRL responses compared with control women.
  
  
  CONCLUSIONS
  The findings that men with major depression exhibit reductions in both protirelin-induced TSH and PRL responses support the hypothesis that TRH receptors are downregulated in depression. The findings in women are less clear and may represent the greater variance in the protirelin-induced PRL responses found in women.
authors.affiliation: Department of Psychiatry, University of North Carolina at Chapel Hill.
authors.forename: J C
authors.initials: JC
authors.lastname: Garbutt
authors.forename: J P
authors.initials: JP
authors.lastname: Mayo
authors.forename: K Y
authors.initials: KY
authors.lastname: Little
authors.forename: G M
authors.initials: GM
authors.lastname: Gillette
authors.forename: G A
authors.initials: GA
authors.lastname: Mason
authors.forename: B
authors.initials: B
authors.lastname: Dew
authors.forename: A J
authors.initials: AJ
authors.lastname: Prange
mesh_terms: D000328:Adult; D003866:Depressive Disorder / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000187:drug effects; D011388:Prolactin / Q000097:blood*; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000187:drug effects; D012737:Sex Factors; D013972:Thyrotropin / Q000097:blood*; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D013972:Thyrotropin; D006854:Hydrocortisone