The effects of hormone replacement therapy on hypothalamic neuropeptide gene expression in a primate model of menopause.
The effects of hormone replacement therapy on hypothalamic neuropeptide gene expression in a primate model of menopause.
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DOI：
10.1210/jcem.84.6.5689
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发表时间：
1999-06
期刊：
影响因子：
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通讯作者：
Ty W. Abel;M. Voytko;N. Rance
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文献类型：
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作者：
Ty W. Abel;M. Voytko;N. Rance
绝经与人下丘脑中神经激肽B（NKB）基因表达增加和阿黑皮素原（POMC）基因表达减少相关。在本研究中，年轻的，卵巢切除的食蟹猴绝经模型中使用的激素替代疗法（HRT）下丘脑神经肽基因表达的影响进行了研究。第二个目标是通过检查POMC神经元和小胶质细胞来确定HRT是否在灵长类动物下丘脑中产生雌激素毒性的迹象。使用合成的放射性标记的48碱基寡核苷酸探针进行原位杂交。α-萘丁酸酯酶组织化学用于可视化小胶质细胞。雌激素和雌激素加孕激素治疗产生了显着抑制漏斗神经元表达NKB基因转录本的数量。与此相反，HRT对神经元的POMC系统或漏斗核中的小胶质细胞的数量没有影响。这些结果为绝经后妇女下丘脑NKB基因表达增加继发于雌激素戒断的假设提供了有力的支持。相反，这些数据表明，老年妇女中表达POMC基因转录本的神经元数量的急剧下降是由卵巢衰竭以外的因素引起的。最后，我们没有发现任何证据表明，HRT，剂量设计模仿目前规定的方案，产生的迹象，雌激素毒性的灵长类动物漏斗核。
Menopause is associated with increased neurokinin B (NKB) gene expression and decreased proopiomelanocortin (POMC) gene expression in the human hypothalamus. In the present study, young, ovariectomized cynomolgus monkeys were used in a model of menopause to examine the effects of hormone replacement therapy (HRT) on hypothalamic neuropeptide gene expression. A secondary goal was to determine whether HRT produces signs of estrogen toxicity in the primate hypothalamus by examining POMC neurons and microglial cells. In situ hybridization was performed using synthetic, radiolabeled, 48-base oligonucleotide probes. Alpha-napthyl butyrate esterase histochemistry was used to visualize microglial cells. Both estrogen and estrogen plus progesterone treatments produced a marked suppression of the number of infundibular neurons expressing NKB gene transcripts. In contrast, HRT had no effect on the POMC system of neurons or the number of microglial cells in the infundibular nucleus. These results provide strong support for the hypothesis that the increased NKB gene expression in the hypothalamus of postmenopausal women is secondary to estrogen withdrawal. Conversely, these data suggest that the dramatic decline in the numbers of neurons expressing POMC gene transcripts in older women is caused by factors other than ovarian failure. Finally, we found no evidence that HRT, in doses designed to mimic currently prescribed regimens, produces signs of estrogen toxicity in the primate infundibular nucleus.