Neuroendocrine aging in the female rat:: The changing relationship of hypothalamic gonadotropin-releasing hormone neurons and N-methyl-D-aspartate receptors
Neuroendocrine aging in the female rat:: The changing relationship of hypothalamic gonadotropin-releasing hormone neurons and N-methyl-D-aspartate receptors
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DOI：
10.1210/en.141.12.4757
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发表时间：
2000-12-01
期刊：
影响因子：
4.8
通讯作者：
Oung, T
中科院分区：
文献类型：
--
作者：
Gore, AC;Yeung, G;Oung, T
生殖轴在衰老过程中发生变化，导致非周期性和生殖功能的丧失。在下丘脑中，GnRH神经元的内在变化可能在这一过程中起关键作用，神经递质（如谷氨酸）对GnRH神经元的输入可能发生变化。我们研究了年龄和生殖状态对雌性大鼠神经内分泌促性腺激素能NMDA受体（NRs）的影响，它们对GnRH神经元的调节，以及它们在GnRH神经元上的表达。首先，我们定量NR亚基信使RNA（mRNA）在视前区-前下丘脑（POA-AH）和内侧基底下丘脑（MBH），GnRH胞体和神经末梢的网站，分别。在POA-AH中，NR 1 mRNA水平随年龄或生殖状态变化不大。NR 2a和NR 2b mRNA水平在周期性和非周期性大鼠之间显著降低。在MBH中，NR mRNA均随着衰老而增加，特别是在无周期动物中。第二，研究了N-甲基-D，L-天冬氨酸（NMA）对衰老大鼠POA-AH中GnRH mRNA水平的影响。NMA升高青年大鼠GnRH mRNA水平，但降低中年大鼠GnRH mRNA水平。第三，我们用免疫细胞化学双标记技术定量测定了衰老大鼠GnRH胞体NR 1亚基的表达。NR 1在GnRH胞体上的表达随年龄和生殖状态而变化，在青年动情前期、中年动情前期和中年持续动情大鼠中，NR 1双标记的GnRH胞体分别为30%、19%和46%。因此，1）下丘脑NR亚基mRNA的表达与生殖状态相关; 2）NR亚基mRNA水平的变化，如果通过蛋白质水平的变化反映，可能导致衰老过程中NR化学计量的改变，并可能产生生理后果; 3）在生殖衰老过程中，NR激活对GnRH mRNA的作用由刺激性转变为抑制性;（4）GnRH胞体NR 1亚基的表达随生殖状态而变化。这些分子，生理和细胞神经内分泌的变化，提出了在老龄雌性大鼠的过渡到非周期性参与。
The reproductive axis undergoes alterations during aging, resulting in acyclicity and the loss of reproductive function. In the hypothalamus, changes intrinsic to GnRH neurons may play a critical role in this process, as may changes in inputs to GnRH neurons from neurotransmitters such as glutamate. We investigated the effects of age and reproductive status on neuroendocrine glutamatergic NMDA receptors (NRs), their regulation of GnRH neurons, and their expression on GnRH neurons, in female rats. First, we quantified NR subunit messenger RNAs (mRNAs) in preoptic area-anterior hypothalamus (POA-AH) and medial basal hypothalamus (MBH), the sites of GnRH perikarya and neuroterminals, respectively. In POA-AH, NR1 mRNA levels varied little with age or reproductive status. NR2a and NR2b mRNA levels decreased significantly between cycling and acyclic rats. In MBH, NR mRNAs all increased with aging, particularly in acyclic animals. Second, we tested the effects of N-methyl-D,L aspartate (NMA) on GnRH mRNA levels in POA-AH of aging rats. NMA elevated GnRH mRNA levels in young rats, but decreased them in middle-aged rats. Third, we quantified expression of the NR1 subunit on GnRH perikarya in aging rats using double label immunocytochemistry. NR1 expression on GnRH cell bodies Varied with age and reproductive status, with 30% , 19%, and 46% of GnRH somata double labeled with NR1 in young proestrous, middle-aged proestrous, and middle-aged persistent estrous rats, respectively. Thus, 1) the expression of hypothalamic NR subunit mRNAs correlates with reproductive status; 2) changes in NR subunit mRNA levels, if reflected by changes in protein levels, may result in alterations in the stoichiometry of the NR during aging, with possible physiological consequences; 3) the effects of NR activation on GnRH mRNA switches from stimulatory to inhibitory during reproductive aging; and 4) expression of the NR1 subunit on GnRH perikarya changes with reproductive status. These molecular, physiological, and cellular neuroendocrine changes are proposed to be involved in the transition to acyclicity in aging female rats.