Melatonin Promotes the Synthesis and Secretion of Growth Hormone in the Adenohypophysis by Activating the cAMP/FOXO1 Pathway

Melatonin, a signaling molecule secreted by the pineal gland, is closely associated with physiological activities, such as animal growth, development, and reproduction. Multiple studies have indicated that melatonin acts on the adenohypophysis to promote the synthesis and secretion of growth hormone (GH), but the specific mechanism of melatonin remains unclear. We have previously reported that melatonin levels in bovine serum are closely correlated with GH levels. In the present study, transcriptome sequencing was performed on primary bovine adenohypophyseal cells treated with melatonin, which identified FOXO1 as a key transcription factor that is responsive to melatonin and regulates GH synthesis and secretion. Cellular experiments revealed that melatonin binds to the MTNR1A in bovine adenohypophyseal cells, activates the cAMP/PKA signaling pathway, and promotes the expression of FOXO1 protein. Dual-luciferase reporter assays verified the binding of FOXO1 to the GH1 promoter. Treatment with Luzindole, 4P-PDOT, 2',5'-Dideoxyadenosine or H-89 elucidated the molecular mechanism through which melatonin promotes GH synthesis and secretion in adenohypophyseal cells through the cAMP/PKA/CREB/FOXO1 pathway. The present study provides critical evidence for the direct action of melatonin on adenohypophyseal cells and its targeted regulatory sites, and it offers new insights into the conserved and species-specific modes of action of melatonin across different species, providing data and theoretical support for the application of melatonin in promoting animal growth and development.