GAMMA-AMINOBUTYRIC-ACID IS AN INHIBITORY NEUROTRANSMITTER RESTRICTINGTHE RELEASE OF LUTEINIZING-HORMONE-RELEASING HORMONE BEFORE THE ONSETOF PUBERTY

To test the hypothesis that the pubertal increase in luteinizing hormo ne-releasing hormone (LHRH) release is withheld by a dominant inhibito ry neuronal system, the role of gamma-aminobutyric acid (GABA), a know n inhibitory neurotransmitter, in the control of LHRH release was exam ined in conscious female monkeys at the prepubertal and pubertal stage s using a push-pull perfusion method. GABA, bicuculline (a GABA(A) rec eptor blocker), and 2-hydroxy-saclofen (a GABA(B) receptor blocker) we re directly infused into the stalk-median eminence while perfusates we re collected for LHRH determination. Bicuculline, but not saclofen, in duced a large and prompt increase in LHRH release in prepubertal monke ys, whereas it stimulated LHRH release slightly in pubertal monkeys. I n contrast, GABA suppressed LHRH release in pubertal, but not prepuber tal, monkeys. These differential effects of GABA and the GABA antagoni st on LHRH release in the two developmental stages were due to an age factor rather than to the steroid hormonal background. Moreover, GABA release in the stalk-median eminence of prepubertal monkeys was much h igher than that in pubertal monkeys. Thus, the results suggest that in the prepubertal period there is a powerful GABA inhibition of the LHR H neurosecretory system: infusions of GABA(A), but not GABA(B), antago nists stimulate LHRH release by removal of the endogenous GABA inhibit ion, whereas exogenous GABA is ineffective because of high endogenous GABA levels. The decrease of this tonic inhibition may be a key factor for the onset of puberty in non-human primates.