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首页> 美国卫生研究院文献>Endocrinology >Hypothalamic IGF-I Gene Therapy Prolongs Estrous Cyclicity and Protects Ovarian Structure in Middle-Aged Female Rats
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Hypothalamic IGF-I Gene Therapy Prolongs Estrous Cyclicity and Protects Ovarian Structure in Middle-Aged Female Rats

机译：下丘脑IGF-I基因治疗延长中年雌性大鼠的发情循环并保护卵巢结构。

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There is substantial evidence that age-related ovarian failure in rats is preceded by abnormal responsiveness of the neuroendocrine axis to estrogen positive feedback. Because IGF-I seems to act as a permissive factor for proper GnRH neuronal response to estrogen positive feedback and considering that the hypothalamic content of IGF-I declines in middle-aged (M-A) rats, we assessed the effectiveness of long-term IGF-I gene therapy in the mediobasal hypothalamus (MBH) of M-A female rats to extend regular cyclicity and preserve ovarian structure. We used 3 groups of M-A rats: 1 group of intact animals and 2 groups injected, at 36.2 weeks of age, in the MBH with either a bicistronic recombinant adeno-associated virus (rAAV) harboring the genes for IGF-I and the red fluorescent protein DsRed2, or a control rAAV expressing only DsRed2. Daily vaginal smears were taken throughout the study, which ended at 49.5 weeks of age. We measured serum levels of reproductive hormones and assessed ovarian histology at the end of the study. Although most of the rats injected with the IGF-I rAAV had, on the average, well-preserved estrous cyclicity as well as a generally normal ovarian histology, the intact and control rAAV groups showed a high percentage of acyclic rats at the end of the study and ovaries with numerous enlarged cysts and scarce corpora lutea. Serum LH was higher and hyperprolactinemia lower in the treated animals. These results suggest that overexpression of IGF-I in the MBH prolongs normal ovarian function in M-A female rats.
机译：有大量证据表明，大鼠年龄相关的卵巢衰竭之前，神经内分泌轴对雌激素阳性反馈的反应异常。由于IGF-I似乎是适当的GnRH神经元对雌激素阳性反馈的允许因子，并考虑到中年（MA）大鼠的IGF-I下丘脑含量下降，因此我们评估了长期IGF-I的有效性我在MA雌性大鼠的中下丘脑（MBH）中进行基因治疗，以延长规则的周期性并保持卵巢结构。我们使用了3组MA大鼠：1组完整动物和2组在36.2周龄时向MBH注射了带有IGF-I基因和红色荧光的双顺反子重组腺相关病毒（rAAV）蛋白DsRed2或仅表达DsRed2的对照rAAV。在整个研究过程中，每天进行阴道涂片检查，该检查在49.5周龄时结束。在研究结束时，我们测量了生殖激素的血清水平并评估了卵巢组织学。尽管平均而言，注射IGF-1 rAAV的大多数大鼠的动情周期均保持良好，并且卵巢组织学一般正常，但完整的rAAV组和对照的rAAV组在末期的无环大鼠中比例较高。研究和卵巢有大量肿大的囊肿和稀有的黄体。在治疗的动物中，血清LH较高而高泌乳素血症则较低。这些结果表明，MBH中IGF-I的过表达延长了M-A雌性大鼠的正常卵巢功能。

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