γ-Aminobutyric Acid Stimulates Pituitary Growth Hormone Secretion in the Neonatal Rat. A Superfusion Study

Abstract

The putative inhibitory neurotransmitter gamma-aminobutyric acid (GABA) elicited a dose-dependent increase in GH secretion from the pituitary of newborn rats. GH secretion increased within 3 min after GABA administration with a peak response at 5-6 min. The lowest effective dose of the GABA agonist muscimol was about 10 times smaller than that of GABA. The GABA effect was antagonized by picrotoxin and bicuculline, suggesting that GABA acts at GABA-A type receptors. The pituitary responsiveness to GABA gradually decreased during the second and third postnatal weeks. If the neonatal pituitaries were continuously exposed to GABA for 3 h GH secretion rapidly increased to a maximum within the first 10 min and then gradually decreased to a less elevated level by 1 h and remained at this level for the next 2 h. After 3 h of GABA exposure muscimol had no effect on GH secretion but human pancreatic GH-releasing factor stimulated it, indicating receptor desensitization during prolonged GABA administration. The significance of GABAergic regulation of GH secretion in the neonate is emphasized by the finding that simultaneous administration of picrotoxin diminished the GH releasing activity of the hypothalamic extract of 2-day-old rats by more than 60%. These results indicate that in the postnatal period the regulation of GH secretion differs from that of the adult animal and GABA might play an important role in the maintenance of the high GH secretion during the first days of life.