Growth hormone/insulin-like growth factor 1 and Alzheimer s disease

19 2 2007 4 Chinese Bulletin of Life Sciences Vol. 19, No. 2 Apr., 2007 1004-0374(2007)02-0208-06 / 1 ( 100850) / -1(GH/IGF-1) (AD) (GH) (GHRH) GH/IGF-1 GH/IGF-1 (AD) GH/IGF-1 AD AD / 1 AD 1 R743 Q575.11 R592 Growth hormone/insulin-like growth factor 1 and Alzheimer s disease ZHANG Ting, SUN Manji* (Institute of Pharmacology and Toxicology, Beijing 100850, China) Abstract: The synthesis, secretion, regulation and biological activity of the growth hormone (GH) / insulin-like growth factor- 1 (IGF-1) play important parts in the development of Alzheimer s disease (AD). The synthesis and secretion are regulated by the stimulants, the GH-releasing hormone (GHRH). Decrement of the activity of the somatotrophic axis causes a series of changes of physiological functions. The deficiency of GH/IGF-1 results in aging and decline of cognition. Supplementation of the related hormones will protect or reverse the cognitive deficits. The evidence available strongly indicates that GH / IGF-1 therapy in Alzheimer s dementia may be addressing pathogenic processes. The role of GH/IGF-1 in the development of Alzheimer s disease and pharmacological research are reviewed Key words: growth hormone; insulin-like growth factor 1; Alzheimer s disease 1 (growth hormone, GH) (GH-releasing hormone GHRH) GH, GH ( 1) GH 50 GH 60 GH GH GH GH (1) IGFs (somatomedin, SM) GH IGFs IGFs (2) 2006-08-01 2006-09-01 (1964 ) (1931 ) * Tel: 010-66874609 E-mail: sunmj@nic.bmi.ac.cn

/ 1 209 GH GH IGF-1 GH GH 12 18h IGF-1 GH IGF-1 GH IGF-1 GH IGF-1 GH/IGF-1 GH DNA mrna IGF (Alzheimer s disease AD) (senile plaque, SP) (neurofibrillary tangles, NFT) AD AD β- (β-amyloid peptide, Aβ) ( SP ) NFT AD AD AD GH/IGF-1 AD 2 GH AD 2.1 AD GH AD (acetylcholine) (dopamine) ( somatostatin) ( noradrenaline) AD Gomez [1] AD (vascular dementia VD) AD VD GH GHRH AD VD AD GH (TSH) CT GHRH GH 28 AD 28 TSH (TRH) [2] Gilles [3] AD GH 1

210 (clonidine) GH SDAT(senile dementia of the Alzheimer type SDAT) GH SDAT GH Lesch [4] AD - - (HPS) - - (HPA),, AD GHRH GH GHRH (ACTH) GHRH GH IGF-1 GHRH GH ACTH GHRH AD (bromocriptine) GH (prolactin PRL) GH DAT(dementia of the Alzhei-mertype) MID (multi-infarct dementia, MID) [5] AD (pyridostigmine) GH GH [6] AD GH AD GH GH IGF-1 10 14% GH LDL-CHol GH (somatopause) [7] GH/IGF-1 DSST (the digit symbol substitution test) CST(the concept shifting task) IGF-1 DSST CST AD GH/IGF-1 [8] AD GH GH [9] GH AD GHRH Vitiello [10] GH [ AD MCI mild cognition impairment)] GH AD GH Aβ AD GH - AD [11] GH GH GH ( ) GH GH 2.2 AD GH GH GH GH, GHRH GH AD (ChEIs) GH GHRH Pirenzepine( M ) GHRH GH [12] GH

/ 1 211 GH AD GH AD IGF-1 GH AD GHRH GH (atropine) DAT GHRH GH AD GH [12-13] ChEIs GH (rivastigmine) ChEI, GHRH ( ) GH (donepezil, AD AD ) GH/IGF-1 GH GHRH GH 53% IGF-1 31% GH/IGF-1 [8] (physostigmine ) SS ( ) GHRH [14] GH GH 3 IGF-1 AD 3.1 AD IGF-1 IGF-1 IGF-1 AD Aβ tau IGF-1 AD IGF-1 IGF-2 IGF-1 IGF-1 IGF-1 [15] IGF-1 CNS DNA RNA AD IGF-1 AD [16] IGF-1 IGF-1 IGF IGF-1/IGF-2 IGF-2 [17] AD IGF-1 IGF-1 [18] TNF-α TNF AD MCI IGF-1 [19] Xing [20] IGF-1 Aβ IGF-1(10 100nmol/L) Aβ amylion IGF-1 Aβ IGF-1 tau (AD ) IGF-1 Aβ Aβ Aβ Tg 2576 IGF-1 Aβ [21-22] Carro Torres-Aleman [21] IGF-1 Aβ Aβ Aβ Aβ IGF-1 AD tau IGF-1 AD AD IGF-1 IGF-1 tau

212 IGF-1 AD [22] IGF-1-3 (glycogen synthase kinase 3, GSK-3) tau IGF-1 GSK-3 tau tau 2(insulin receptor substrate, IRS-2) IGF-1 IGF-1 IRS-2 IGF-1 tau IGF-1 tau IGF-1 [21-23] IGF-1 ( IGF-1 ) IGF-1 (insulin-like growth factor-1 binding proteins, IGFBPs) IGF-1 IGF-1 IGFBPs IGF-1 IGF-1 IGF-1 [24] IGF-1 IGF Aβ tau IGF-1 IGF-1 3.2 IGF-1 AD GH IGF-1 GH, IGF-1, GH IGF-1 GH GH GH IGF-1 [25] APP/PS2 Aβ precursor protein (APP) presenilin (PS)-2 Aβ IGF-1 Aβ AD IGF-1 Aβ ( J ) Aβ Aβ IGF-1 APP IGF-1 AD [26] IGF-1 GH GH 1B [27] 4 GH / IGF-1 AD GH IGF-1 (GHD) (turner syndrome, TS) (intra uterirne growth retardation, IUGR) (central precocious puberty, CPP) (famillia short stature, FSS) GH GH ( imidazoline ) IGF-1 AD IGF-1 IGF-1 IGF-1 AD IGF-1 IGF-1 GHRH IGF-1 ( IGFBPs IGF-1) AD IGF-1 GH AD [1] Gomez I M, Aguilar M, Navarro M A, et al. GH response to GH-releasing hormone (GHRH) in Alzheimer and vascular dementia. Relation with somatostatin cerebrospinal levels. Ann Endocrinol (Paris), 1996, 57(2): 107-110 [2] Gomez J M, Aguilar M, Soler J. Growth hormone and thyrotropin hormone secretion in Alzheimer's disease. J Nutr Health Aging, 2000, 4(4): 229-232 [3] Gilles C, Ryckaert P, De Mol J, et al. Clonidine-induced growth hormone secretion in elderly patients with senile dementia of the Alzheimer type and major depressive disorder. Psychiatry Res, 1989, 27(3): 277-286 [4] Lesch K P, Ihl R, Frolich L. Endocrine responses to growth hormone releasing hormone and corticotropin releasing hormone in early-onset Alzheimer's disease. Psychiatry Res, 1990, 33(2): 107-112 [5] Higashi S, Fujita M, Nishimoto Y, et al. Neuroendocrine studies in dementia patients: responses of plasma GH and PRL following bromocriptine administration. Acta Neurol Scand, 1994, 90(1): 39-44 [6] van Amelsvoort T, Murphy D G, Robertson D, et al. Effects of long-term estrogen replacement therapy on growth hormone response to pyridostigmine in healthy postmeno-

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