Changes in prodynorphin gene expression and neuronal morphology in the hypothalamus of postmenopausal women.
Changes in prodynorphin gene expression and neuronal morphology in the hypothalamus of postmenopausal women.
复制标题
绝经后妇女下丘脑强啡肽原基因表达和神经元形态的变化。
DOI：
10.1111/j.1365-2826.2008.01796.x
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发表时间：
2008
影响因子：
3.2
通讯作者：
Rance,NE
中科院分区：
文献类型：
--
作者：
Rometo,AM;Rance,NE
人类更年期的特点是卵巢功能衰竭，促性腺激素分泌增加，下丘脑漏斗状核(弓状核)内表达神经激动素B(NkB)、KiSS-1和雌激素受体(ER)α基因转录的神经元肥大。在实验动物的弓状核，强啡肽是一种阿片肽，与NkB、Kispeptin、ERα和孕激素受体共定位。此外，卵巢切除降低了母羊弓状核中前强啡肽基因转录本的表达。因此，我们假设绝经后妇女漏斗核内肥大的神经元表达强啡肽原基因，并推测绝经后伴随强啡肽原基因转录产物的改变。在本研究中，使用针对前强啡肽mRNA的放射性标记的cDNA探针，对绝经前和绝经后妇女的下丘脑切片进行了原位杂交。用放射自显影和计算机辅助显微镜对标记的神经元进行定位和计数，测量神经元大小，并比较绝经前和绝经后组前强啡肽基因的表达。绝经后妇女漏斗核强啡肽基因表达神经元体积较大，形态特征为肥大。此外，与绝经前组相比，绝经后组漏斗核内前强啡肽探针标记的神经元较少。绝经后妇女的内侧视前/下丘脑前区强啡肽mRNA表达神经元的数量也减少了，但细胞大小没有变化。在下丘脑其他区域，强啡肽mRNA表达神经元的细胞数量和大小没有观察到差异。以前使用动物模型的研究提供了强有力的证据，表明绝经后妇女前强啡肽神经元大小和基因表达的变化是绝经后卵巢衰竭的继发性改变。考虑到强啡肽对生殖轴的抑制作用，强啡肽基因表达减少可能在绝经后妇女黄体激素分泌增加中起作用。
Human menopause is characterised by ovarian failure, gonadotrophin hypersecretion and hypertrophy of neurones expressing neurokinin B (NKB), kisspeptin (KiSS)‐1 and oestrogen receptor (ER) α gene transcripts within the hypothalamic infundibular (arcuate) nucleus. In the arcuate nucleus of experimental animals, dynorphin, an opioid peptide, is colocalised with NKB, kisspeptin, ERα and progesterone receptors. Moreover, ovariectomy decreases the expression of prodynorphin gene transcripts in the arcuate nucleus of the ewe. Therefore, we hypothesised that the hypertrophied neurones in the infundibular nucleus of postmenopausal women would express prodynorphin mRNA and that menopause would be accompanied by changes in prodynorphin gene transcripts. In the present study,in situhybridisation was performed on hypothalamic sections from premenopausal and postmenopausal women using a radiolabelled cDNA probe targeted to prodynorphin mRNA. Autoradiography and computer‐assisted microscopy were used to map and count labelled neurones, measure neurone size and compare prodynorphin gene expression between premenopausal and postmenopausal groups. Neurones expressing dynorphin mRNA in the infundibular nucleus of the postmenopausal women were larger and exhibited hypertrophied morphological features. Moreover, there were fewer neurones labelled with the prodynorphin probe in the infundibular nucleus of the postmenopausal group compared to the premenopausal group. The number of dynorphin mRNA‐expressing neurones was also reduced in the medial preoptic/anterior hypothalamic area of postmenopausal women without changes in cell size. No differences in cell number or size of dynorphin mRNA‐expressing neurones were observed in any other hypothalamic region. Previous studies using animal models provide strong evidence that the changes in prodynorphin neuronal size and gene expression in postmenopausal women are secondary to the ovarian failure of menopause. Given the inhibitory effect of dynorphin on the reproductive axis, decreased dynorphin gene expression could play a role in the elevation in luteinising hormone secretion that occurs in postmenopausal women.