Rapid modulation of TRH and TRH-like peptide levels in rat brain and peripheral tissues by corticosterone.
Disturbance of glucocorticoid signaling has been implicated in several neuropsychiatric disorders including unipolar and bipolar depression and anxiety induced by maternal deprivation. Antidepressants have been shown to be neuroprotective and able to reverse damage to glia and neurons. Thyrotropin-releasing hormone (TRH) is an endogenous antidepressant that reduces the expression of glycogen synthase kinase-3beta (GSK-3beta), an enzyme that hyperphosphorylates tau and is implicated in bipolar depression, diabetes and Alzheimer's disease. In order to understand the potential role of TRH and TRH-like peptides both as mediators of the depressogenic effects of glucocorticoids and as potential therapeutics for neuropsychiatric disease, 300 g male Sprague-Dawley rats were injected i.p. with 4 mg corticosterone/0.5 ml 50% DMSO+50% ethanol and sacrificed 0, 2, 4 and 8h later. Levels of TRH and TRH-like peptides were measured in various brain regions involved in mood regulation and pancreas and reproductive tissues that mediate the metabolic and reproductive impairments associated with high glucocorticoid levels. Significant increases, ranging from 2- to 12-fold, in TRH or TRH-like peptide levels were observed in almost all brain regions studied at 4h after corticosterone injection. In cerebellum, TRH and TRH-like peptides increased 4-14-fold by 8h. TRH-like peptide levels fell 86-98% at 4h after treatment in testis. TRH, derived only from Leydig cells, was not affected. TRH and TRH-like peptides increased 2-4-fold at 8h in pancreas. TRH and TRH-like peptide concentrations in prostate were not affected by corticosterone up to 8h after injection. The 4h needed to detect a highly significant change in the TRH and TRH-like peptide levels in brain and peripheral tissues is consistent with the mediation of most corticosterone-effects via alterations in gene transcription.
Pekary
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Research Services, VA Greater Los Angeles Healthcare System, Building 114, Room 229, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA. eugene.pekary@med.va.gov
Stevens
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SA
Sattin
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D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009929:Organ Size; D010455:Peptides / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*
D010455:Peptides; D013973:Thyrotropin-Releasing Hormone; D003345:Corticosterone