(-)-DEPRENYL TREATMENT RESTORES SERUM INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) LEVELS IN AGED RATS TO YOUNG-RAT LEVEL

We studied the effects of treatment with (-)-deprenyl, a monoamine oxi dase B inhibitor, on plasma levels of insulin-like growth factor-I (IG F-I) (as indicator of growth hormone (GH) secretion), levels of monoam ines and their metabolites, and the activity and content of tyrosine h ydroxylase - the rate-limiting enzyme in the biosynthesis of catechola mines - in the hypothalamus and hypophysis of old male rats. Male Wist ar rats (22 months old) were treated with 2 mg deprenyl/kg body weight s.c. three times a week for 2 months. At the end of the treatment per iod, blood was collected for measurement of plasma IGF-I levels by rad ioimmunoassay (RIA). The concentrations of dopamine, serotonin (5-HT) and their main metabolites were determined by high performance liquid chromatography (HPLC) with electrochemical detection, and the tyrosine hydroxylase content in hypothalamus and hypophysis was determined by enzyme-linked immunoabsorbent assay (ELISA). (-)-Deprenyl treatment pr oduced a pronounced increase in dopamine and 5-HT in both the hypothal amus and hypophysis (P < 0.01). The main dopaminergic metabolite, 3,4- dihydroxyphenylacetic acid (DOPAC), decreased in hypothalamus but not in hypophysis, and treatment had no effect on the concentration of 5-h ydroxyindole-3-acetic acid (5-HIAA). The tyrosine hydroxylase activity and tyrosine hydroxylase content increased in hypothalamus and hypoph ysis (P < 0.05). In the hypophysis the increase in tyrosine hydroxylas e activity was consistent with the increase in tyrosine hydroxylase am ount. Moreover, (-)-deprenyl treatment restored the IGF-I plasma level s in old rats to a concentration similar to those found in young anima ls. Postulated anti-aging effects of(-)-deprenyl could hence be due to restoration of hypothalamic hormones such as GH.