GABA OF CNS ORIGIN IN THE RAT ANTERIOR-PITUITARY INHIBITS PROLACTIN SECRETION

Hypothalamic hormones synthesised in nuclei within the medial basal hypothalamus (MBH) and extrahypothalamic regions and released from nerve endings at the level of the median eminence (ME) into the hypophysial portal capillary system control anterior pituitary (AP) function. The median eminence is a key area for neuroendocrine regulation as it receives projections of neurotransmitter pathways which modulate functions such as synthesis and release of hypothalamic hormones. In addition, transmitters released from the ME into the stalk portal blood may act directly at the AP level to control hormone secretion-this has been demonstrated for dopamine (DA) with respect to prolactin (PRL) secretion and it has been suggested that DA itself may represent the so far elusive PRL-inhibiting factor (PIF). Recently, evidence has been presented which suggests that γ-aminobutyric acid (GABA) may also have an important inhibitory role in regulating PRL secretion in the rat. Both GABA and muscimol, a powerful agonist at GABA receptors, inhibited PRL secretion when injected into urethane anaesthetised female or freely moving male rats. In view of the poor penetrability of the blood-brain barrier (BBB) by both amino acids and the recently described specific GABA receptor sites in rat AP, the above data support the notion that GABA may act directly at the level of the AP to inhibit PRL secretion. This proposition is reinforced by the demonstration that both GABA and muscimol inhibit PRL secretion from rat isolated APs, an effect which is blocked by the antagonist picrotoxin. We report here that GABA, derived from the central nervous system (CNS), is present in the rat anterior pituitary, and we provide evidence that GABA has a functional role in the control of PRL secretion.