期刊
NEUROPHARMACOLOGY
卷 58, 期 1, 页码 314-320出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2009.06.015
关键词
Aging; Kisspeptin; GPR54; Hypothalamus; AVPV; Arcuate nucleus
资金
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [U54HD058155] Funding Source: NIH RePORTER
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [R01HD029856] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [T32AG023475] Funding Source: NIH RePORTER
- NIA NIH HHS [T32 AG23475, T32 AG023475] Funding Source: Medline
- NICHD NIH HHS [L50 HD051440-01, L50 HD051440, L50 HD051440-02, R01 HD029856-12, R01 HD029856-11, R01 HD29856, R01 HD029856, R01 HD029856-13, R01 HD029856-13S1, R01 HD029856-14, U54 HD058155] Funding Source: Medline
Female reproductive aging in rats is characterized by reduced gonadotropin releasing hormone (GnRH) neuronal activation under estradiol positive feedback conditions and a delayed and attenuated luteinizing hormone (LH) surge. The newly identified excitatory neuropeptide kisspeptin is proposed to be a critical mediator of the pubertal transition and the ovarian steroid-induced LH surge. We previously showed that estradiol induces less kisspeptin mRNA expression in the anterior hypothalamus [anatomical location of anteroventral periventricular nucleus (AVPV)] in middle-aged than in young rats and intrahypothalamic infusion of kisspeptin restores LH surge amplitude in middle-aged females. Thus, reduced kisspeptin neurotransmission may contribute to age-related LH surge abnormalities. This study tested the hypothesis that middle-aged females will also exhibit reduced numbers of kisspeptin immunopositive neurons in the AVPV under estradiol positive feedback conditions. Using immunohistochemistry, we demonstrate that middle-aged females primed with ovarian steroids have fewer AVPV kisspeptin immunopositive neurons than young females. Age did not affect kisspeptin mRNA expression in the pituitary, numbers of kisspeptin immunopositive neurons in the arcuate nucleus, or estradiol-dependent reductions in kisspeptin mRNA expression in the posterior hypothalamus (containing the arcuate nucleus). These data strongly suggest that age-related LH surge dysfunction results, in part, from a reduced sensitivity of AVPV kisspeptin neurons to estradiol and hence decreased availability of AVPV kisspeptin neurons to activate GnRH neurons under positive feedback conditions. (C) 2009 Elsevier Ltd. All rights reserved.
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