Allopregnanolone and dehydroepiandrosterone response to corticotropin-releasing factor in patients suffering from Alzheimer's disease and vascular dementia

• Published in: European journal of endocrinology Vol. 142; no. 5; pp. 466 - 471
• Main Authors: Bernardi, F, Lanzone, A, Cento, RM, Spada, RS, Pezzani, I, Genazzani, AD, Luisi, S, Luisi, M, Petraglia, F, Genazzani, AR
• Format: Journal Article
• Language: English
• Published: Colchester European Society of Endocrinology 01.05.2000; Portland Press
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - blood; Area Under Curve; Biological and medical sciences; Case-Control Studies; Corticotropin-Releasing Hormone; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dehydroepiandrosterone - blood; Dementia, Vascular - blood; Female; GABA Modulators - blood; Humans; Hydrocortisone - blood; Male; Medical sciences; Middle Aged; Neurology; Pregnanolone - blood; Human; Nervous system diseases; Vascular dementia; Androgen; Pathophysiology; Alzheimer disease; Corticotropin releasing factor; Hydrocortisone; Glucocorticoid; Pregnanolone; Cerebral disorder; Hypothalamic hormone; Dehydroepiandrosterone; Adrenal hormone; Central nervous system disease; Hormonal regulation; Degenerative disease; Hormone releasing factor; Sex steroid hormone; Elderly; Cerebrovascular disease; Hypothalamohypophysocorticoadrenal axis
• ISSN: 0804-4643; 1479-683X
• DOI: 10.1530/eje.0.1420466

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). DESIGN: 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.