ROLE OF THE NEURONAL HISTAMINERGIC SYSTEM IN THE REGULATION OF SOMATOTROPIC FUNCTION - COMPARISON BETWEEN THE NEONATAL AND THE ADULT-RAT

To study possible age-related differences in the role of neuronal hist aminergic pathways in the control of GH secretion, the effects of alph a-fluoromethylhistidine (alpha-FMH), an irreversible inhibitor of hist amine (HA) synthesis, were examined on basal and opioid-induced GH rel ease in neonatal and adult rats. The mechanisms involved in such effec ts were evaluated by measuring pituitary GH mRNA levels and hypothalam ic levels of GH-releasing hormone (GHRH) and somatostatin (SRIF) mRNAs . Daily injec tion of alpha-FMH (20 mg/kg, s.c.) in pups of either sex , from birth until 10 days of age, caused a significant increase in ba seline plasma GH and potentiated the GH response to the [Met(5)]-enkep halin analog FK 33-824 (1 mg/kg, s.c.) administered 3 h after the last alpha-FMH injection. GH and SRIF mRNA levels were significantly highe r in alpha-FMH-treated pups than in controls, whereas no difference wa s observed in GHRH mRNA levels. In young adult male rats, acute admini stration of alpha-FMH (100 mg/kg, s.c., 3 h before) did not change sig nificantly basal GH levels but potentiated FK 33-824 (0.3 mg/kg, intra carotid)-induced stimulation of GH secretion. Repeated administration of alpha-FMH (200 mu g/rat, i.c.v., for 3 days) failed to modify basal and FK 33-824-induced GH secretion, caused a significant reduction in hypothalamic GHRH mRNA levels and left SRIF and GH mRNAs unchanged. T hese findings indicate that HA exerts an inhibitory effect on GH secre tion in both neonatal and adult rats. The different effects of short-t erm HA depletion on hypothalamic and pituitary indices of somatotropic function observed at the two age periods may be ascribed to the immat urity of the HA system in early postnatal life and to a different func tional role of GH-regulatory factors during ontogeny.