Estrogen receptor-alpha immunoreactivity in the arcuate hypothalamus of young and middle-aged female mice

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.