Rapid modulation of TRH and TRH-like peptide release in rat brain and peripheral tissues by leptin.

Leptin is not only a feedback modulator of feeding and energy expenditure but also regulates reproductive functions, CNS development and mood. Obesity and major depression are growing public health concerns which may derive, in part, from disregulation of leptin feedback at the level of the hypothalamic feeding centers and mood regulators within the limbic system. Identifying downstream mediators of leptin action may provide therapeutic opportunities. We and others have previously reported that thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH(2)) and TRH-like peptides (pGlu-X-Pro-NH(2), where "X" can be any amino acid residue) have neuroprotective, antidepressant, anti-epileptic, analeptic, anti-ataxic, and anorectic properties. For this reason, young, adult male Sprague-Dawley rats were injected ip with 1mg/kg rat leptin and peptide and protein levels were measured in brain and peripheral tissues at 0, 0.5, 1 and 2h later. Eleven brain regions: pyriform cortex (PYR), entorhinal cortex (ENT), cerebellum (CBL), nucleus accumbens (NA), frontal cortex (FCX), amygdala (AY), posterior cingulate (PCNG), striatum (STR), hippocampus (HC), medulla oblongata (MED) and anterior cingulate (ACNG) and five peripheral tissues (adrenals, testes, epididymis, pancreas and prostate) were analyzed. TRH and six TRH-like peptide levels in STR fell by 0.5h consistent with leptin-induced release of these peptides: STR (7 downward arrow). Significant changes in TRH and TRH-like peptide levels for other brain regions were: CBL (5 downward arrow), ENT (5 downward arrow), HC (4 downward arrow), AY (4 downward arrow), FCX (3 downward arrow), and ACNG (1 downward arrow). The rapid modulation of TRH and TRH-like peptide release combined with their similarity in behavioral, neuroendocrine, immunomodulatory, metabolic and steroidogenic effects to that of leptin is consistent with these peptides participating in downstream signaling.