Yaghmaie Farzin, Saeed Omar, Garan Steven A, Voelker Mark A, Sternberg Hal, Timiras Paola S
Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Neuro Endocrinol Lett. 2010;31(1):56-62.
Changes in the neuroendocrine regulation of gonadal function, via altered hypothalamic sensitivity to peripheral hormones, are known to schedule reproductive maturation in the young and influence reproductive senescence. Estrogen (E) is a key hormone in this process. While changes in circulating levels of E over the life span are well documented, less is known about the corresponding changes in E sensitivity over the lifespan, especially during middle-age, when the initial signs of reproductive senescence emerge.
Taking Estrogen Receptor (ER)-alpha-immunoreactive cells as an index of hypothalamic sensitivity to E, this investigation aims to quantify alterations occurring at middle age in comparison to young age.
We counted ER-alpha-immunoreactive (IR) cells in the Arcuate hypothalamus of 6-week-old (young) and 18-month-old (middle-aged) C57BL/6J female mice, sacrificed at vaginal opening and diestrous, respectively. An automated imaging microscopy system (AIMS) was employed to generate counts of ER-alpha-IR cells for each sampled section of the Arcuate nucleus (ARC).
This study shows a 21% reduction in the number of ER-alpha-IR cells and an 18% reduction in total ARC cell populations with aging. However, the calculated percentage of ER-alpha IR cells is similar in both young and middle aged mice, 30% and 29%, respectively.
Both ER-alpha IR cell populations and total cell populations within the ARC hypothalamus decline by middle age in comparison to young age. Despite such a significant decrease in ER-alpha immunoreactive and total cells, both young and middle age mice maintain a similar ratio of ER-alpha IR cells to total cells in the ARC hypothalamus.
已知通过改变下丘脑对外周激素的敏感性，性腺功能的神经内分泌调节变化可安排年轻人的生殖成熟并影响生殖衰老。雌激素（E）是这一过程中的关键激素。虽然E在整个生命周期中循环水平的变化已有充分记录，但对于E敏感性在整个生命周期中的相应变化了解较少，尤其是在中年，此时生殖衰老的最初迹象开始出现。
以雌激素受体（ER）-α免疫反应性细胞作为下丘脑对E敏感性的指标，本研究旨在量化中年与年轻相比发生的变化。
我们分别在6周龄（年轻）和18月龄（中年）C57BL/6J雌性小鼠的弓状下丘脑计数ER-α免疫反应性（IR）细胞，分别在阴道开口期和动情间期处死小鼠。采用自动成像显微镜系统（AIMS）对弓状核（ARC）的每个采样切片中的ER-α-IR细胞进行计数。
本研究表明，随着年龄增长，ER-α-IR细胞数量减少21%，ARC总细胞数量减少18%。然而，计算得出的ER-α IR细胞百分比在年轻和中年小鼠中相似，分别为30%和29%。
与年轻相比，中年时ARC下丘脑内的ER-α IR细胞群体和总细胞群体均减少。尽管ER-α免疫反应性细胞和总细胞数量显著减少，但年轻和中年小鼠在ARC下丘脑内的ER-α IR细胞与总细胞的比例相似。
