Changes in Indole Metabolism in Organ Cultured Rat Pineal Glands Induced by Interferon‐γ

The purpose of this study was to test the effects of recombinant rat interferon‐γ (IFN‐γ) on rat pineal function in orgran culture. The glands were pre‐incubated with IFN‐γ (50, 100, and 1,000 antiviral units/ml) for two hours, followed by a stimulation with isoproterenol (ISO, 10^‐6M) (in the presence of IFN‐γ) for an additional three hours. The effect of IFN‐γ alone on the pineal function was also tested by adding another group incubated with IFN‐γ (1,000 antiviral units/ml) without ISO stimulation. The following parameters were estimated at the end of the incubation: the activities of N‐acetyltransferase (NAT) and hydroxyindole‐O‐methyltransferase (HIOMT), the levels of melatonin, 5‐hydroxytryptophan (5HTP), 5‐hydroxytryptamine (5HT), and 5‐hydroxyindole acetic acid (5HIAA), and the 5HT/5HIAA ratio. IFN‐γ had no effect on either NAT or HIOMT activities in the pineal glands. At 50 units/ml, IFN‐γ increased the melatonin content over the ISO‐stimulated level in the pineal but not in the media. IFN‐γ alone, at 1,000 units/ml, also increased the melatonin content significantly over the control level. The levels of 5HTP and 5HIAA were significantly suppressed by IFN‐γ, either alone or in combination with ISO. The level of 5HT was not altered by any of the treatments. The 5HT/5HIAA ratio was significantly increased by IFN‐γ, either when given alone or when given in combination with ISO. The results suggest that IFN‐γ enhances melatonin production in the pineal gland by suppressing the oxidative deamination of 5HT to 5HIAA and shunting the biosynthetic pathway toward melatonin production.