title: Roles of estrogen receptor-alpha in mediating life span: the hypothalamic deregulation hypothesis.
abstract: In several species caloric restriction (CR) extends life span. In this paper we integrate data from studies on CR and other sources to articulate the hypothalamic deregulation hypothesis by which estrogen receptor-alpha (ER-α) signaling in the hypothalamus and limbic system affects life span under the stress of CR in mammals. ER-α is one of two principal estrogen-binding receptors differentially expressed in the amygdala, hippocampus, and several key hypothalamic nuclei: the arcuate nucleus (ARN), preoptic area (POA), ventromedial nucleus (VMN), antero ventral periventricular nucleus (AVPV), paraventricular nucleus (PVN), supraoptic nucleus (SON), and suprachiasmatic nucleus (SCN). Estradiol signaling via ER-α is essential in basal level functioning of reproductive cycle, sexually receptive behaviors, physiological stress responses, as well as sleep cycle, and other nonsexual behaviors. When an organism is placed under long-term CR, which introduces an external stress to this ER-α signaling, the reduction of ER-α expression is attenuated over time in the hypothalamus. This review paper seeks to characterize the downstream effects of ER-α in the hypothalamus and limbic system that affect normal endocrine functioning.
authors.affiliation: Lawrence Berkeley National Laboratories, Berkeley, California.|Center for Research and Education in Aging, University of California at Berkeley, Lawrence Berkeley National Laboratories, California; and.|Department of Integrative Biology, University of California at Berkeley, Berkeley, California.
authors.forename: Arvin M
authors.initials: AM
authors.lastname: Gouw
authors.affiliation: Lawrence Berkeley National Laboratories, Berkeley, California.|Center for Research and Education in Aging, University of California at Berkeley, Lawrence Berkeley National Laboratories, California; and.
authors.forename: Gizem
authors.initials: G
authors.lastname: Efe
authors.affiliation: Lawrence Berkeley National Laboratories, Berkeley, California.|Center for Research and Education in Aging, University of California at Berkeley, Lawrence Berkeley National Laboratories, California; and.
authors.forename: Rita
authors.initials: R
authors.lastname: Barakat
authors.affiliation: Lawrence Berkeley National Laboratories, Berkeley, California.|Center for Research and Education in Aging, University of California at Berkeley, Lawrence Berkeley National Laboratories, California; and.
authors.forename: Andrew
authors.initials: A
authors.lastname: Preecha
authors.affiliation: Lawrence Berkeley National Laboratories, Berkeley, California.|Center for Research and Education in Aging, University of California at Berkeley, Lawrence Berkeley National Laboratories, California; and.
authors.forename: Morvarid
authors.initials: M
authors.lastname: Mehdizadeh
authors.affiliation: Lawrence Berkeley National Laboratories, Berkeley, California.|Center for Research and Education in Aging, University of California at Berkeley, Lawrence Berkeley National Laboratories, California; and.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Garan
authors.affiliation: Center for Research and Education in Aging, University of California at Berkeley, Lawrence Berkeley National Laboratories, California; and gbrooks@berkeley.edu.|Department of Integrative Biology, University of California at Berkeley, Berkeley, California.
authors.forename: George A
authors.initials: GA
authors.lastname: Brooks
mesh_terms: D000818:Animals; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D008136:Longevity; D008954:Models, Biological; D012727:Sex Characteristics; D013312:Stress, Physiological
chemical_list: D047628:Estrogen Receptor alpha
keywords: HPG axis; caloric restriction; circadian rhythms; estrogen receptor; hypothalamus; limbic system; longevity; sexual behavior; sexual dimorphism; stress response