Luteinizing hormone: Evidence for direct action in the CNS

This article is part of a Special Issue “SBN 2014”.Hormonal dysfunction due to aging, especially during menopause, plays a substantial role in cognitive decline as well as the progression and development of neurodegenerative diseases. The hypothalamic–pituitary–gonadal (HPG) axis has long been implicated in changes in behavior and neuronal morphology. Most notably, estrogens have proven beneficial in the healthy brain through a host of different mechanisms. Recently, luteinizing hormone (LH) has emerged as a candidate for further investigation for its role in the CNS. The basis of this is that both LH and the LH receptor are expressed in the brain, and serum levels of LH correlate with cognitive deficits and Alzheimer's disease (AD) incidence. The study of LH in cognition and AD primarily focuses on evaluating the effects of downregulation of this peptide. This literature has shown that decreasing peripheral LH, through a variety of pharmacological interventions, reduces cognitive deficits in ovariectomy and AD models. However, few studies have researched the direct actions of LH on neurons and glial cells. Here we summarize the role of luteinizing hormone in modulating cognition, and we propose a mechanism that underlies a role for brain LH in this process.

In the aged female brain estrogen replacement after ovariectomy does not improve cognitive function or associated underlying mechanisms such as dendritic spine density changes. Drugs that reduce peripheral levels of LH, which surge after ovariectomy or during menopause, rescue ovariectomy-dependent cognitive dysfunction, increases signaling events associated with synaptic plasticity. The LH receptor is localized to cognition-associated areas and its functionality is described both at a level of function and plasticity. Brain-derived LH protein levels are present in cognition associated areas and reduced by ovariectomy. These levels are normalized by drugs that reduce peripheral LH levels and this normalization of brain-LH positively correlates with markers of neuroplasticity and cognitive improvement.Figure optionsDownload high-quality image (114 K)Download as PowerPoint slide