LIM homeobox transcription factor Isl1 is required for melatonin synthesis in the pig pineal gland

Isl1 knockdown in cultured primary porcine pinealocytes results in a decline of melatonin levels by 29.2% and AANAT mRNA levels by 72.2%.

• Isl1 is highly expressed in melatonin-producing cells in the porcine pineal gland.
• Isl1 overexpression increases melatonin levels by 1.3-fold and AANAT mRNA levels by 2.7-fold.
• Norepinephrine enhances melatonin synthesis, an effect that is abolished by Isl1 knockdown.
• Intracerebroventricular norepinephrine injections increase Isl1 mRNA and protein levels by about threefold and 4.5-fold, respectively.
• Isl1 protein levels are 2.5-fold higher at 24:00 compared to 12:00, correlating with melatonin levels.
• Isl1 positively modulates melatonin synthesis by targeting AANAT through the ERK signaling pathway activated by norepinephrine.

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