Evidence that interferon-γ alters pineal metabolism both indirectly via sympathetic nerves and directly on the pinealocytes

Abstract

1. 1. Interferon-γ (IFN-γ) has been shown to suppress N-acetyltransferase (NAT) activity in cultured rat pineal glands when stimulated with isoproterenol (ISO). 2. 2. Conversely, IFN-γ has also been shown to increase the melatonin content of the rat pineal gland in organ culture. 3. 3. Circumstantial evidence leads to a hypothesis that the NAT suppressive effect may be due to the action of IFN-γ on the sympathetic nerve terminals. 4. 4. To test this hypothesis, pineal glands from intact (INT) and superior cervical ganglionectomized (SCGX) rats, which had been operated 5 days earlier, were cultured with either ISO or ISO + IFN-γ. 5. 5. The concentration of ISO was 10 −8 M and that of IFN-γ was 300 antiviral units/ml. 6. 6. The pineals were incubated for a total period of 5.5 hr, after which the activities of NAT and hydroxyindole- O-methyltransferase (HIOMT) and the levels of melatonin and cAMP were estimated. 7. 7. Suppression of NAT by IFN-γ was observed in the pineals from INT rats, but not in those from SCGX animals. 8. 8. IFN-γ significantly enhanced melatonin levels over those in ISO-stimulated pineals and culture media from the SCGX animals, but not from the INT animals. 9. 9. IFN-γ treatment had no effect on either the HIOMT activity or cAMP levels. 10. 10. The results indicate that the IFN-γ-induced NAT suppression requires the integrity of the sympathetic nerve terminals and the IFN-γ-induced enhancement of melatonin production is accomplished through its direct action on pinealocytes.