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 histaminergic pathways in the control of GH secretion, the effects of alpha-fluoromethylhistidine (alpha-FMH), an irreversible inhibitor of histamine (HA) synthesis, were examined on basal and opioid-induced GH release in neonatal and adult rats. The mechanisms involved in such effects were evaluated by measuring pituitary GH mRNA levels and hypothalamic levels of GH-releasing hormone (GHRH) and somatostatin (SRIF) mRNAs. Daily injection 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 baseline plasma GH and potentiated the GH response to the [Met5]-enkephalin 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 higher in alpha-FMH-treated pups than in controls, whereas no difference was observed in GHRH mRNA levels. In young adult male rats, acute administration of alpha-FMH (100 mg/kg, s.c., 3 h before) did not change significantly basal GH levels but potentiated FK 33-824 (0.3 mg/kg, intracarotid)-induced stimulation of GH secretion. Repeated administration of alpha-FMH (200 micrograms/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. These findings indicate that HA exerts an inhibitory effect on GH secretion in both neonatal and adult rats. The different effects of short-term HA depletion on hypothalamic and pituitary indices of somatotropic function observed at the two age periods may be ascribed to the immaturity of the HA system in early postnatal life and to a different functional role of GH-regulatory factors during ontogeny.
Grilli
R
R
Department of Pharmacology, School of Medicine, University of Milan, Italy.
Sibilia
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V
Torsello
A
A
Pagani
F
F
Guidi
M
M
Luoni
M
M
Netti
C
C
Müller
E E
EE
D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000494:pharmacology; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics; D006633:Histamine Antagonists / Q000494:pharmacology*; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008762:Methylhistidines / Q000494:pharmacology*; D010902:Pituitary Gland / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000235:genetics; D015430:Weight Gain / Q000187:drug effects
D006633:Histamine Antagonists; D008762:Methylhistidines; D012333:RNA, Messenger; D013004:Somatostatin; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; C028309:alpha-fluoromethylhistidine; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D006640:Histidine Decarboxylase