title: Allopregnanolone and dehydroepiandrosterone response to corticotropin-releasing factor in patients suffering from Alzheimer's disease and vascular dementia.
abstract: OBJECTIVE
  Neurosteroids have been suggested to be involved in the regulation of cognitive performances. A major neurosteroid gamma-aminobutyric acid (GABA) agonist is allopregnanolone: the main source of circulating allopregnanolone is the adrenal cortex. Studies indicated that a disturbance of the central regulation of the hypothalamic-pituitary-adrenocortical axis occurs in both senile (Alzheimer's disease: AD) and vascular dementia (VD).
  
  
  METHODS
  The aim of the present study was to evaluate the levels of circulating allopregnanolone, dehydroepiandrosterone (DHEA) and cortisol and their response to corticotropin-releasing factor (CRF) test in AD and VD.
  
  
  METHODS
  Three groups of 12 subjects were included in the study: AD, VD and age-matched control subjects. CRF test was performed in all subjects and allopregnanolone, DHEA and cortisol levels were measured every 15min for 2h.
  
  
  RESULTS
  Mean +/- s.e.m. allopregnanolone and DHEA basal levels were significantly lower in AD and VD than in controls, while cortisol levels were significantly higher than in controls (P<0.01). Allopregnanolone and DHEA levels increase in response to CRF test in all subjects but the area under curve (AUC) in patients was significantly lower than in controls (P<0.01). Cortisol secretion appeared to be very sensitive in response to CRF stimulation: in fact, cortisol response to CRF test in AD and VD subjects was higher (both as AUC and as % max increase) than in controls (P<0.01).
  
  
  CONCLUSIONS
  The present study firstly showed that allopregnanolone levels are reduced both in AD and in VD and that dementia has a preserved stimulated response of allopregnanolone to CRF. Overall, however, the total response of allopregnanolone to CRF remains reduced in respect to controls. Further studies are necessary for a better understanding of the role of neurosteroids in the regulation of cognitive function.
authors.affiliation: Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bernardi
authors.forename: A
authors.initials: A
authors.lastname: Lanzone
authors.forename: R M
authors.initials: RM
authors.lastname: Cento
authors.forename: R S
authors.initials: RS
authors.lastname: Spada
authors.forename: I
authors.initials: I
authors.lastname: Pezzani
authors.forename: A D
authors.initials: AD
authors.lastname: Genazzani
authors.forename: S
authors.initials: S
authors.lastname: Luisi
authors.forename: M
authors.initials: M
authors.lastname: Luisi
authors.forename: F
authors.initials: F
authors.lastname: Petraglia
authors.forename: A R
authors.initials: AR
authors.lastname: Genazzani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D019540:Area Under Curve; D016022:Case-Control Studies; D003346:Corticotropin-Releasing Hormone; D003687:Dehydroepiandrosterone / Q000097:blood*; D015140:Dementia, Vascular / Q000097:blood*; D005260:Female; D018757:GABA Modulators / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011280:Pregnanolone / Q000097:blood*
chemical_list: D018757:GABA Modulators; D003687:Dehydroepiandrosterone; D003346:Corticotropin-Releasing Hormone; D011280:Pregnanolone; D006854:Hydrocortisone