INIBIOLP-Pathology B, UNLP, La Plata, Argentina.
Department of Histology and of Embryology B, UNLP, La Plata, Argentina.
Curr Gene Ther. 2018;18(4):240-245. doi: 10.2174/1566523218666180905170020.
Insulin-like Growth Factor1 (IGF1) is a powerful neuroprotective molecule. We have previously shown that short-term hypothalamic IGF1 gene therapy restores tuberoinfundibular dopaminergic neuron function in aging female rats.
Our aim was to implement long-term IGF-I gene therapy in pituitary prolactinomas in senile female rats.
Here, we assessed the long-term effect of IGF1 gene therapy in the hypothalamus of young (4 mo.) and aging (24 mo.) female rats carrying spontaneous pituitary prolactinomas. We constructed and injected a Helper-Dependent (HD) adenovector expressing the gene for rat IGF1 or the reporter red fluorescent protein DsRed. Ninety-one days post vector injection, all rats were sacrificed and their brains and pituitaries fixed. Serum prolactin (PRL), Estrogen (E2) and progesterone (P4), as well as hypothalamic IGF1 content, were measured by RIA. Anterior pituitaries were immunostained with an anti-rat PRL antibody and submitted to morphometric analysis.
DsRed expression in the Mediobasal Hypothalamus (MBH) was strong after the treatment in the DsRed group while IGF1 content in the MBH was higher in the IGF1 group. The IGF1 treatment affected neither pituitary weight nor PRL, E2 or P4 serum levels in the young rats. In the old rats, IGF1 gene therapy reduced gland weight as compared with intact counterparts and tended to reduce PRL levels as compared with intact counterparts. The treatment significantly rescued the phenotype of the lactotropic cell population in the senile adenomas.
We conclude that long-term hypothalamic IGF1 gene therapy is effective to rescue spontaneous prolactinomas in aging female rats.
胰岛素样生长因子 1（IGF1）是一种强大的神经保护分子。我们之前已经表明，短期下丘脑 IGF1 基因治疗可恢复衰老雌性大鼠的结节漏斗多巴胺能神经元功能。
我们的目的是在衰老雌性大鼠的垂体泌乳素瘤中实施 IGF-I 基因的长期治疗。
在这里，我们评估了 IGF1 基因治疗对携带自发性垂体泌乳素瘤的年轻（4 个月）和衰老（24 个月）雌性大鼠下丘脑的长期影响。我们构建并注射了一种表达大鼠 IGF1 基因或报告红色荧光蛋白 DsRed 的 Helper-Dependent（HD）腺病毒载体。载体注射后 91 天，所有大鼠均被处死，并固定其大脑和垂体。通过 RIA 测量血清泌乳素（PRL）、雌激素（E2）和孕激素（P4）以及下丘脑 IGF1 含量。用抗大鼠 PRL 抗体对垂体前叶进行免疫染色，并进行形态计量学分析。
DsRed 表达在治疗后 DsRed 组的中脑基底部（MBH）很强，而 IGF1 含量在 IGF1 组的 MBH 中更高。IGF1 治疗对年轻大鼠的垂体重量或 PRL、E2 或 P4 血清水平均无影响。在老年大鼠中，IGF1 基因治疗与完整对照组相比降低了腺体重量，并倾向于降低与完整对照组相比的 PRL 水平。该治疗显著挽救了衰老腺瘤中催乳细胞群的表型。
我们得出结论，长期下丘脑 IGF1 基因治疗可有效挽救衰老雌性大鼠的自发性泌乳素瘤。
