Melatonin and environmental lighting regulate ALA-S gene expression and So porphyrin biosynthesis in the rat harderian gland.

The main porphyrin in rodent Harderian glands (HGs) is the heme precursor protoporphyrin IX (PPIX). Rhythmic variations in PPIX levels have yet to be studied in rodent HGs. Moreover, the mode of regulation of heme biosynthesis in this organ is poorly documented in the rat. The aim of this study was to determine day-night PPIX levels as well as day-night activity and mode of expression of the porphyrinogenic enzymes delta-aminolevulinate synthase (ALA-S) and ferrochelatase (Fech) in the rat HG. The mRNA expression of ABCG2/Bcrp1 was also investigated. Male Wistar rats acclimatized to 12 h light (L): 12 h dark (D) cycles were sacrificed in the middle of both the L and D spans, and HG and liver tissues were collected. We report here that the HG contains an extremely high level of PPIX, 630- to 670-fold higher than in the liver, without a day-night difference, which is the consequence of both low Fech gene expression (5- to 7-fold lower than in the liver) and ALA-S over-expression (4- to 7-fold higher in the HG than liver). Fech and PPIX transporter ABCG2/Bcrp1 do not exhibit day-night variation, whereas HG ALA-S levels are significantly higher during the scotophase. Interestingly, when melatonin (10 mg/kg) is administered in the middle of the light phase, it increases ALA-S mRNA levels in the HG to the ones observed during the middle of the D span. Continuous light exposure abolishes the day-night ALA-S variation in the HG that is observed under standard 12 L:12 D conditions. Our results suggest that melatonin and environmental lighting regulate ALA-S gene expression in the rat HG.