Luteinizing hormone downregulation but not estrogen replacement improves ovariectomy-associated cognition and spine density loss independently of treatment onset timing.

Age-related changes in reproductive hormone levels are a well-known risk factor for the development of cognitive dysfunction and dementia in women. We and others have shown an important contribution of gonadotropins in this process. Lowering serum gonadotropin levels is able to rescue cognitive function in Alzheimer's disease and menopause models, but whether this is time-dependent and the exact mechanism through which gonadotropins regulate cognitive function is unknown. We show that pharmacologically lowering serum levels of luteinizing hormone lead to cognitive improvement immediately after ovariectomy and with a 4month interval after ovariectomy, when the benefits of 17ß-estradiol are known to disappear in rodents. Importantly, we show that these improvements are associated with spine density changes at both time points. These findings suggest a role of luteinizing hormone in learning and memory and neuroplasticity processes as well as provide an alternative therapeutic strategy of menopause associated cognitive loss.

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.