Biochemical and functional aspects on the control of prolactin release by the hypothalamo-pituitary GABAergic system

A growing body of biochemical, immunohistochemical, and autoradiographic evidence indicates the presence of two different GABAergic systems in the mediobasal hypothalamus: one intrinsic, the tuberoinfundibular GABAergic system, and the other extrinsic, whose cell bodies are located outside the mediobasal hypothalamus and which projects to this area and establishes synaptic contacts with aminergic and peptidergic neurons involved in endocrine function. This particular anatomical configuration provides a rational basis to explain the dual action of GABA (inhibitory and stimulatory) on prolactin release. Different studies aimed at identifying the precise role of GABA on prolactin function have demonstrated that this system can be modulated, at the pre- and/or post-synaptic level, by different experimental maneuvers in which prolactin secretion is physiologically and pharmacologically altered. GABA mainly appears to be involved in feedback mechanisms preventing an exaggerated prolactin output during specific physiological situations. The ability of clinically tested, direct GABAmimetic compounds to lower prolactin secretion in the rat points towards a clinical usefulness of these drugs in particular spontaneous or induced neuroendocrine disorders. However, the possibility of a widespread use of this type of compounds is hampered by the lack of potent, specific and non-toxic GABA agonists suitable for clinical purposes.