Estrogens, progestins, menopause and neurodegeneration: basic and clinical studies

被引:66
作者
Simpkins, JW [1 ]
Yang, SH [1 ]
Wen, Y [1 ]
Singh, M [1 ]
机构
[1] Univ N Texas, Ctr Hlth Sci, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA
关键词
estrogens; progestins; neuroprotection; stroke; Alzheimer disease; ischemia; estrogen receptor;
D O I
10.1007/s00018-004-4382-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Two classes of ovarian steroids, estrogens and progestins, are potent in protecting neurons against acute toxic events as well as chronic neurodegeneration. Herein we review the evidence for neuroprotection by both classes of steroids, provide plausible mechanisms for these potent neuroprotective activities and indicate the need for further clinical trials of both estrogens and progestins in protection against acute and chronic conditions that cause neuronal death. Estrogens at concentrations ranging from physiological to pharmacological are neuroprotective in a variety of in vitro and in vivo models of cerebral ischemia and brain trauma as well as in reducing key neuropathologies of Alzheimer's disease. While the mechanisms of this potent neuroprotection are currently unresolved, a mitochondrial mechanism is involved. Progestins have been recently shown to activate many of the signaling pathways used by estrogens to neuroprotect, and progestins have been shown to protect against neuronal loss in vitro and in vivo in a variety of models of acute insult. Collectively, results of these animal and tissue culture models suggest that the loss of both estrogens and progestins at the menopause makes the brain more vulnerable to acute insults and chronic neurodegenerative diseases. Further clinical assessment of appropriate regimens of estrogens, progestins and their combination are supported by these data.
引用
收藏
页码:271 / 280
页数:10
相关论文
共 111 条
[1]   Gender-linked brain injury in experimental stroke [J].
Alkayed, NJ ;
Harukuni, I ;
Kimes, AS ;
London, ED ;
Traystman, RJ ;
Hurn, PD .
STROKE, 1998, 29 (01) :159-165
[2]  
ALKJAERSIG N, 1988, J LAB CLIN MED, V111, P224
[3]   Progesterone facilitates the acquisition of avoidance learning and protects against subcortical neuronal death following prefrontal cortex ablation in the rat [J].
Asbury, ET ;
Fritts, ME ;
Horton, JE ;
Isaac, WL .
BEHAVIOURAL BRAIN RESEARCH, 1998, 97 (1-2) :99-106
[4]   Neuroprotection against oxidative stress by estrogens: Structure-activity relationship [J].
Behl, C ;
Skutella, T ;
Lezoualch, F ;
Post, A ;
Widmann, M ;
Newton, CJ ;
Holsboer, F .
MOLECULAR PHARMACOLOGY, 1997, 51 (04) :535-541
[5]   PROGESTIN ANTAGONISM OF ESTROGEN STIMULATED 1,25-DIHYDROXYVITAMIN-D LEVELS [J].
BIKLE, DD ;
HALLORAN, BP ;
HARRIS, ST ;
PORTALE, AA .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1992, 75 (02) :519-523
[6]   ESTRADIOL TREATMENT INCREASES VIABILITY OF GLIOMA AND NEUROBLASTOMA-CELLS IN-VITRO [J].
BISHOP, J ;
SIMPKINS, JW .
MOLECULAR AND CELLULAR NEUROSCIENCE, 1994, 5 (04) :303-308
[7]   Transgenic mouse models of Alzheimer's disease and amyotrophic lateral sclerosis [J].
Borchelt, DR ;
Wong, PC ;
Sisodia, SS ;
Price, DL .
BRAIN PATHOLOGY, 1998, 8 (04) :735-757
[8]   Subcellular distribution of native estrogen receptor α and β subtypes in cultured human lens epithelial cells [J].
Cammarata, PR ;
Chu, SY ;
Moor, A ;
Wang, ZH ;
Yang, SH ;
Simpkins, JW .
EXPERIMENTAL EYE RESEARCH, 2004, 78 (04) :861-871
[9]   Estrogen status affects sensitivity to focal cerebral ischemia in stroke-prone spontaneously hypertensive rats [J].
Carswell, HVO ;
Dominiczak, AF ;
Macrae, IM .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2000, 278 (01) :H290-H294
[10]   Neuroprotective effects of progesterone on damage elicited by acute global cerebral ischemia in neurons of the caudate nucleus [J].
Cervantes, M ;
González-Vidal, MD ;
Ruelas, R ;
Escobar, A ;
Moralí, G .
ARCHIVES OF MEDICAL RESEARCH, 2002, 33 (01) :6-14