Effects of age on beta 1- and beta 2-adrenergic receptors in the brain assessed by quantitative autoradiography.

Effects of age on beta 1- and beta 2-adrenergic receptors in the brain assessed by quantitative autoradiography.
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通过定量放射自显影评估年龄对大脑中 β1- 和 β2- 肾上腺素能受体的影响。

DOI:
10.1016/0006-8993(86)91490-3
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发表时间:
1986
期刊:
影响因子:
2.9
通讯作者:
Wise,PM
Wise,PM
中科院分区:
医学3区
文献类型:
--
作者:
Weiland,NG;Wise,PM

文献摘要

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衰老雌性大鼠的生殖周期丧失与特定下丘脑区域中去甲肾上腺素神经元活性的改变相关,该区域参与促性腺激素分泌的调节。我们探讨了生殖功能恶化也可能是由于结合和介导对去甲肾上腺素反应的受体密度变化的可能性。现有证据表明,β-肾上腺素能受体介导去甲肾上腺素对促黄体生成素(LH)的抑制作用。因此,我们确定β-肾上腺素能受体密度的变化是否发生在与生殖功能相关的特定下丘脑核团。此外,我们希望确定年龄是否不同地影响β1和β2肾上腺素能受体密度,以及受体密度的年龄相关变化是否与动物的激素状态和/或阴道涂片细胞学相关。在1000 h时处死老年持续发情大鼠、老年持续性间情大鼠、发情期青年周期大鼠和发情期青年周期大鼠,采用局部放射自显影和计算机图像分析方法测量脑β1-和β2-肾上腺素能受体密度,这些方法允许高水平的神经解剖学区分。我们分析了7个脑区(包括4个已知在生殖功能中重要的下丘脑区域)的β1和β2肾上腺素能受体密度。检查了松果体、小脑的分子层和尾壳核,因为它们含有高浓度的β-肾上腺素能受体,据报道这些受体随年龄变化。在相同的大鼠中测定血清促黄体生成素。无论阴道涂片细胞学检查和年龄如何,所有大鼠的血清LH浓度均相同。在视前内侧核,老年大鼠β1肾上腺素能受体密度增加。相反,在视交叉上核中,老年大鼠的β2-肾上腺素能受体较低。我们没有观察到任何受体亚型在正中隆起或乳头体前核的年龄相关的变化。松果体中β1和β2肾上腺素能受体浓度均降低,而小脑中仅β2受体随年龄增长而降低。在尾壳核中未观察到年龄相关的差异。在任何检查的区域,在发情期和间情期之间,未观察到年轻或老年雌性动物的β-肾上腺素能受体密度存在差异。这些数据表明,随着年龄的增长,β受体密度发生了多种多样的变化。它们只发生在选定的大脑区域,并不局限于一种受体亚型。无论阴道细胞学和激素环境如何,持续性发情和持续性发情的老年大鼠都发生了类似的年龄相关变化。
Aging female rats undergo a loss of reproductive cyclicity that has been correlated with alterations in norepinephrine neuronal activity in specific hypothalamic regions involved in the regulation of gonadotropin secretion. We explored the possibility that deteriorating reproductive function may also be due to changes in the density of receptors which bind and mediate responsiveness to norepinephrine. Existing evidence suggests that β-adrenergic receptors mediate norepinephrine's inhibitory effect on luteinizing hormone (LH). Therefore, we determined whether changes in β-adrenergic receptor densities occur in specific hypothalamic nuclei associated with reproductive function. Furthermore, we wished to determine whether age affectsβ1-andβ2-adrenergic receptor densities differentially and whether age-related changes in receptor densities are related to hormonal status and/or vaginal smear cytology of the animals. Old constant estrous rats, old persistent diestrous rats, young cycling rats on estrus, and young cycling rats on diestrus were killed at 1000 h and brainβ1-andβ2-adrenergic receptor densities were measured using topical autoradiographic and computerized image analysis methods which permit a high level of neuroanatomical discrimination. We analyzedβ1-andβ2-adrenergic receptor densities in 7 brain areas including 4 hypothalamic regions known to be important in reproductive function. The pineal gland, the molecular layer of the cerebellum and the caudate putamen were examined because they contain high concentrations of β-adrenergic receptors which have been reported to change with age. Serum luteinizing hormone was measured in the same rats. Serum LH concentrations were the same in all rats regardless of vaginal smear cytology and age. In the medial preoptic nucleus,β1-adrenergic receptor densities were elevated in old rats. In contrast, in the suprachiasmatic nucleusβ2-adrenergic receptors were lower in old rats. We observed no age-associated changes in either receptor subtype in median eminence or premammillary nucleus. Bothβ1-andβ2-adrenergic receptor concentrations decreased in the pineal gland, while onlyβ2-receptors declined with age in the cerebellum. No age-related differences were observed in the caudate putamen. No differences in β-adrenergic receptor densities were seen between estrus and diestrus in either young or old females in any of the areas examined. These data demonstrate that multiple and diverse alterations in β-receptor densities occur with age. They occur only in selected brain regions and are not confined to one receptor subtype. Similar age-associated changes occurred in both persistent diestrous and constant estrous old rats regardless of vaginal cytology and hormonal milieu.