Direct Exposure of Guinea Pig CNS to Human Luteinizing Hormone Increases Cerebrospinal Fluid and Cerebral Beta Amyloid Levels

Background/Aims: Luteinizing hormone (LH) has been shown to alter the metabolism of beta amyloid (A beta), a key protein in Alzheimer's disease (AD) pathogenesis. While LH and components required for LH receptor signalling are present in the brain, their role in the CNS remains unclear. In vitro, LH has been shown to facilitate neurosteroid production and alter A beta metabolism. However, whether LH can directly modulate cerebral A beta levels in vivo has not previously been studied. In this study, we investigated the effect of chronic administration of LH to the guinea pig CNS on cerebral A beta levels. Methods: Gonadectomised male animals were administered, via cortical placement, either placebo or LH slow-release pellets. At 14 and 28 days after treatment, animals were sacrificed. Brain, plasma and CSF were collected and A beta levels measured via ELISA. Levels of the A beta precursor protein (APP) and the neurosteroidogenic enzyme cytochrome P450 side-chain cleavage enzyme (P450scc) were also assayed. Results: An increase in CSF A beta 40 levels was observed 28 days following treatment. These CSF data also reflected changes in A beta 40 levels observed in brain homogenates. No change was observed in plasma A beta 40 levels but APP and its C-terminal fragments (APP-CTF) were significantly increased in response to LH exposure. Protein expression of P450scc was increased after 28 days of LH exposure, suggesting activation of the LH receptor. Conclusion: These data indicate that direct exposure of guinea pig CNS to LH results in altered brain A beta levels, perhaps due to altered APP expression/metabolism. Copyright (C) 2011 S. Karger AG, Basel