Stereologic Analysis of Estrogen Receptor Alpha (ERα) Expression in Rat Hypothalamus and Its Regulation by Aging and Estrogen

The estrogen receptor alpha (ERα) in the hypothalamus plays important roles in the regulation of reproductive development, physiology, and behavior. However, the expression of the ERα may change during aging or in response to varying estrogen levels. The present study measured changes in the numbers of ERα-expressing cells in specific hypothalamic and preoptic nuclei of ovariectomized female Sprague-Dawley rats at three ages (young [3-4 months], middle-aged [10-12 months], or old [24-26 months]) and with or without estrogen replacement. Numbers of ERα-immunoreactive neurons were quantified in four regions relevant to reproductive function: the anteroventral periventricular nucleus (AVPV), medial preoptic nucleus (MPN), arcuate nucleus (ARH), and ventromedial nucleus (VMN), using an unbiased stereologic approach. In the AVPV and VMN, significant age-related increases in the numbers of ERα-expressing cells from the middle-aged to the old group were detected, and no differences were observed in the MPN and ARH, indicating that ERα neuron number is maintained or even elevated during aging. No significant effects of estrogen on ERα cell number were detected in any of the four regions studied. Therefore, ERα cell number in the rat hypothalamus and preoptic area changes with aging in a region-specific manner.