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

被引:63
作者
Bernardi, F
Lanzone, A
Cento, RM
Spada, RS
Pezzani, I
Genazzani, AD
Luisi, S
Luisi, M
Petraglia, F
Genazzani, AR
机构
[1] Univ Pisa, Dept Reprod Med & Child Dev, Sect Gynecol & Obstet, I-56100 Pisa, Italy
[2] Dept Obstet & Gynecol, Oasi, Troina, Italy
[3] Univ Udine, Chair Obstet & Gynecol, Dept Surg Sci, I-33100 Udine, Italy
[4] Univ Modena, Inst Obstet & Gynecol, I-41100 Modena, Italy
[5] Endocrine Res Unit, CNR, Pisa, Italy
关键词
D O I
10.1530/eje.0.1420466
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 15 min for 2 h. 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 buth in AD and in VD and that dementia has a preserved stimulated response of allopregnanolone to CRE 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.
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页码:466 / 471
页数:6
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