title: Direct exposure of guinea pig CNS to human luteinizing hormone increases cerebrospinal fluid and cerebral beta amyloid levels.
abstract: OBJECTIVE
  Luteinizing hormone (LH) has been shown to alter the metabolism of beta amyloid (Aβ), 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 Aβ metabolism. However, whether LH can directly modulate cerebral Aβ 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 Aβ 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 Aβ levels measured via ELISA. Levels of the Aβ precursor protein (APP) and the neurosteroidogenic enzyme cytochrome P450 side-chain cleavage enzyme (P450scc) were also assayed.
  
  
  RESULTS
  An increase in CSF Aβ40 levels was observed 28 days following treatment. These CSF data also reflected changes in Aβ40 levels observed in brain homogenates. No change was observed in plasma Aβ40 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.
  
  
  CONCLUSIONS
  These data indicate that direct exposure of guinea pig CNS to LH results in altered brain Aβ levels, perhaps due to altered APP expression/metabolism.
authors: Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
authors: Eka J
authors: EJ
authors: Wahjoepramono
authors: Linda K
authors: LK
authors: Wijaya
authors: Kevin
authors: K
authors: Taddei
authors: Kristyn A
authors: KA
authors: Bates
authors: Matthew
authors: M
authors: Howard
authors: Georgia
authors: G
authors: Martins
authors: Karl
authors: K
authors: deRuyck
authors: Paul M
authors: PM
authors: Matthews
authors: Giuseppe
authors: G
authors: Verdile
authors: Ralph N
authors: RN
authors: Martins
mesh_terms: D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D006168:Guinea Pigs; D006624:Hippocampus / Q000378:metabolism; D007986:Luteinizing Hormone / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D007986:Luteinizing Hormone; D002786:Cholesterol Side-Chain Cleavage Enzyme