Title
Gonadotropin-releasing hormone receptor system : modulatory role in aging and neurodegeneration Gonadotropin-releasing hormone receptor system : modulatory role in aging and neurodegeneration
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
Subject
Pharmacology. Therapy
Human medicine
Source (journal)
CNS and neurological disorders drug targets
Volume/pages
9(2010) :5 , p. 651-660
ISSN
1871-5273
ISI
000284620800013
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Abstract
Receptors for hormones of the hypothalamic-pituitary-gonadal axis are expressed throughout the brain. Age-related decline in gonadal reproductive hormones cause imbalances of this axis and many hormones in this axis have been functionally linked to neurodegenerative pathophysiology. Gonadotropin-releasing hormone (GnRH) plays a vital role in both central and peripheral reproductive regulation. GnRH has historically been known as a pituitary hormone; however, in the past few years, interest has been raised in GnRH actions at non-pituitary peripheral targets. GnRH ligands and receptors are found throughout the brain where they may act to control multiple higher functions such as learning and memory function and feeding behavior. The actions of GnRH in mammals are mediated by the activation of a unique rhodopsin-like G protein-coupled receptor that does not possess a cytoplasmic carboxyl terminal sequence. Activation of this receptor appears to mediate a wide variety of signaling mechanisms that show diversity in different tissues. Epidemiological support for a role of GnRH in central functions is evidenced by a reduction in neurodegenerative disease after GnRH agonist therapy. It has previously been considered that these effects were not via direct GnRH action in the brain, however recent data has pointed to a direct central action of these ligands outside the pituitary. We have therefore summarized the evidence supporting a central direct role of GnRH ligands and receptors in controlling central nervous physiology and pathophysiology.
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