It has been established that excitatory amino acids (EAAs), such as glutamate and aspartate, are pivotal elements in the hypothalamic circuitry involved in the control of pituitary function. The actions of EAAs are mediated by receptor subtypes, which include ionotropic (NMDA, kainate, AMPA) and three groups of metabotropic glutamate receptors (mGluR). Glutamate and aspartate are found in large concentrations in a variety of important hypothalamic nuclei.
EAA neurotransmission is an essential component of the neuroendocrine transmission line that regulates anterior pituitary luteinizing hormone (LH) and follicle-stimulating hormone secretion. More recently,EAA have been implied in the control of prolactin release.
The physiological importance of EAAs in the control of prolactin secretion is evidenced by the findings that the suckling-induced and the stress-induced prolactin surges and the preovulatory prolactin surge are blocked by treatment with NMDA or non-NMDA receptor antagonists. Administration of glutamate, NMDA, kainate or AMPA leads to prolactin release. The major site of glutamate action appears to be the hypothalamus.
In this review, we summarize our experimental work on the role of EAAs neurotransmission in the control of prolactin secretion in the rat. Recent work of our group has focused on mechanisms whereby glutamatergic circuits interact with neurotransmitters and neuropeptides that controls prolactin secretion such as dopamine, GABA, oxytocin, alpha-melanocyte-stimulating hormone (α-MSH) and substance P. Our data suggest a major role for glutamate in controlling increases in the secretion of prolactin by not only stimulating prolactin release from lactotropes, but also by inhibiting the activity of hypothalamic dopaminergic and GABAergic neurons. The increase of stimulatory factors such as oxytocin, α-MSH and substance P may also contribute to the stimulatory action of glutamate on prolactin release.
D-Aspartate is an endogenous D-aminoacid that participates in the regulation of several endocrine gland functions in mammals. D-aspartate might have a role in neuroendocrine modulation. We reported that this aminoacid has a direct stimulatory effect on prolactin release from anterior pituitary cells. In the hypothalamus, D-aspartate stimulated luteinizing hormone-releasing hormone (LHRH), α-MSH and GABA release and inhibited dopamine release through interaction with NMDA receptors.
In conclusion, our data provide evidence for a pivotal role of glumate and D-aspartate pathways in the regulation of prolactin secretion.
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