Glucagon-Like Peptide (GCGL) Is a Novel Potential TSH-Releasing Factor (TRF) in Chickens: I) Evidence for Its Potent and Specific Action on Stimulating TSH mRNA Expression and Secretion in the Pituitary

Our recent study proposed that the novel glucagon-like peptide (GCGL), encoded by a glucagonlike gene identified in chickens and other lower vertebrates, is likely a hypophysiotropic factor in nonmammalian vertebrates. To test this hypothesis, in this study, we investigated the GCGL action on chicken pituitaries. The results showed that: 1) GCGL, but not TRH, potently and specifically stimulates TSH secretion in intact pituitaries incubated in vitro or in cultured pituitary cells monitored by Western blotting or a cell-based luciferase reporter assay; 2) GCGL (0.1nM-10nM) dose dependently induces the mRNA expression of TSH beta but not 5 other hormone genes in cultured pituitary cells examined by quantitative real-time RT-PCR, an action likely mediated by intracellular adenylate cyclase/cAMP/protein kinase A and phospholipase C/inositol 1,4,5-trisphosphate/Ca2+ signaling pathways coupled to GCGL receptor (GCGLR); 3) GCGLR mRNA is mainly localized in pituitary cephalic lobe demonstrated by in situ hybridization, where TSH-cells reside, further supporting a direct action ofGCGLon thyrotrophs. The potent and specific action ofGCGLon pituitary TSH expression and secretion, togetherwiththepartialaccordanceshownamongthetemporalexpressionprofilesofGCGL in the hypothalamus and GCGLR and TSH beta in the pituitary, provides the first collective evidence that hypothalamic GCGL is most likely to be a novel TSH-releasing factor functioning in chickens. The discovery of this novel potential TSH-releasing factor (GCGL) in a nonmammalian vertebrate species, ie, chickens, would facilitate our comprehensive understanding of the hypothalamic control of pituitary-thyroid axis across vertebrates.