Cp. Delacruz et al., (-)-DEPRENYL TREATMENT RESTORES SERUM INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) LEVELS IN AGED RATS TO YOUNG-RAT LEVEL, European journal of pharmacology, 327(2-3), 1997, pp. 215-220
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.