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Cross-Talk between Excitatory and Inhibitory Amino Acids in the Regulation of Growth Hormone Secretion in Neonatal Rats

Experiments were carried out in 5-day-old male and female rats in order to assess the respective roles of distinct γ-aminobutyric acid (GABA) receptor subtypes in the control of growth hormone (GH) secretion in the newborn rat and to identify the potential sexual dimorphism of GABA actions on GH release. The interplay of GABA and excitatory acids (EAAs) to control GH secretion was also analysed. Effects of specific GABAA, GABAB and GABAC agonists upon GH secretion as well as of co-administration of GABA and agonists and antagonists of EAA receptors were monitored in 5-day-old male rats. The data confirm that GABA stimulates GH secretion in 5-day-old rats, but indicate that the effect is sexually dimorphic, being greater in females. Stimulation of GH secretion by GABA is mainly mediated by GABAA receptors, while GABAC appears to be ineffective. Stimulatory effects of GH by GABA and muscimol, a GABAA receptor agonist, are blocked by pretreatment with (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclophepten-5-10-imine hydrogen maleate (MK-801), an antagonist of N-methyl-D-aspartate (NMDA) receptors, but not by 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]-quinoxaline-7-sulfonamide (NBQX), an antagonist of (±)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors. Simultaneous administration of GABA and NMDA was additive on GH release while basal GH secretion was not affected by either bicuculline or the respective blockers of GABAA and GABAB receptors. In conclusion, our results suggest that cross-talk between inhibitory (GABA) and EAAs is involved in the control of GH secretion in neonates.