Growth hormone receptor knockout mice (GHRKO) have reduced body size and increased insulin sensitivity. These mice are known for having extended lifespan, healthspan and female reproductive longevity. Seventeen α-estradiol (17α-E2) is reported to increase insulin sensitivity and extend lifespan in male mice, with less robust effects in female mice. The aim of this study was to evaluate the ovarian reserve in wild type and GHRKO mice treated with 17α-E2. The mice were divided into four groups, GHRKO mice receiving a standard chow diet, GHRKO mice treated 17α-E2, wild type mice receiving a standard chow diet and WT mice treated with 17α-E2. 17α-E2 was provided in the diet for four months. IGF1 plasma concentrations and changes in body weight were assessed. Histological slides were prepared from the ovaries and the number of follicles was counted. GHRKO mice receiving the control diet had a greater number of primordial follicles and lower numbers of primary follicles compared to the other groups (p < 0.05). 17α-E2 treatment decreased the number of primordial follicles in GHRKO mice (p < 0.05), however had no effect in wild type mice. Treatment with 17α-E2 had no significant effect on the change in body weight during the experiment (p = 0.75). Plasma IGF1 concentrations were significantly lower in GHRKO mice as compared to wild type. In conclusion, we found that GHRKO mice displayed lesser primordial follicle activation as compared to wild type mice, but this phenotype was reversed by 17α-E2 administration, suggesting that ovarian aging is increased by 17α-E2 in long-living mice with extended reproductive longevity.

中文翻译：

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17α-雌二醇可促进生长激素受体敲除小鼠的卵巢衰老，但不促进野生型同窝仔。

生长激素受体敲除小鼠（GHRKO）的体型减小了，胰岛素敏感性增强了。这些小鼠以延长的寿命，健康的寿命和女性的生殖寿命而著称。据报道，在雄性小鼠中有十七种α-雌二醇（17α-E2）可以增加胰岛素敏感性并延长寿命，而在雌性小鼠中则没有那么强的作用。这项研究的目的是评估用17α-E2处理的野生型和GHRKO小鼠的卵巢储备。将小鼠分为四组：接受标准食物的GHHRKO小鼠，处理17α-E2的GHRKO小鼠，接受标准食物的野生型小鼠和用17α-E2处理的WT小鼠。在饮食中提供17α-E2四个月。评估了IGF1血浆浓度和体重变化。从卵巢制备组织学玻片并计数卵泡数。与其他组相比，接受对照饮食的GHRKO小鼠的原始卵泡数量更多，而初级卵泡数量则更少（p <0.05）。17α-E2处理可减少GHRKO小鼠的原始卵泡数量（p <0.05），但在野生型小鼠中无作用。在实验过程中，用17α-E2处理对体重变化无明显影响（p = 0.75）。与野生型相比，GHRKO小鼠的血浆IGF1浓度显着降低。总之，我们发现与野生型小鼠相比，GHRKO小鼠的原始卵泡活化程度较低，但是这种表型被17α-E2所逆转，这表明17α-E2可以延长生殖寿命长寿小鼠的卵巢衰老。 。