The roles of GnRH in the human central nervous system

Abstract

It is widely known that GnRH plays a role in facilitating reproductive function via the HPG axis, and this was once believed to be its only function. However, over the last several decades important neuromodulatory roles of GnRH in multiple brain functions have been elucidated. Multiple GnRH isoforms and receptors have been detected outside the HPG-axis across different species. In this review, we focus on the human CNS where GnRH I and II isoforms and a functional GnRH I receptor have been isolated. We first describe the traditional understanding of GnRH within the hypothalamus and the pituitary and current clinical use of GnRH analogues. We then review the location and function of GnRH-producing neurons and receptors located outside the HPG axis. We next review the GnRH I and II neuron location and quantity and GnRH I receptor gene expression throughout the human brain, using the Allen Brain Map Atlas. This analysis demonstrates a wide expression of GnRH throughout the brain, including prominent expression in the basal forebrain and cerebellum. Lastly, we examine the potential role of GnRH in aging and inflammation and its therapeutic potential for neurodegenerative disease and spinal cord lesions.

Keywords: Aging; Alzheimer's disease; GnRH I; GnRH II; GnRH receptor; Neurodegenerative disease.

Conflict of interest statement

Declaration of competing interest None.

Copyright © 2022 Elsevier Inc. All rights reserved.

Figures

Fig. 1.

Expression of GnRH neuronal isoforms in the adult human brain. The data is presented in z-scores. Value of 0 means average expression, negative means underexpression, and positive numbers means overexpression, compared to the brain as a whole.