Age-related changes in hypothalamic androgen receptor and estrogen receptor alpha in male rats

The control of reproductive function involves actions of sex steroids upon their nuclear receptors in the hypothalamus and preoptic area (POA). Whether hypothalamic hormone receptors change their expression in aging male mammals has not been extensively pursued, although such changes may underlie functional losses in reproductive physiology occurring with aging. We performed a stereologic analysis of immunoreactive androgen receptor (AR) and estrogen receptor alpha (ERalpha) cells in three POA nuclei of male Sprague-Dawley rats (anteroventral periventricular nucleus [AVPV], median preoptic area [MePO], and medial preoptic nucleus [MPN]), at young (3 months), middle-aged (12 months), and old (20 months) ages. Serum testosterone and estradiol levels were assayed. Testosterone concentrations decreased significantly and progressively with aging. Estradiol concentrations were significantly higher in middle-aged than either young or old rats. Stereologic analyses of the POA demonstrated that AR-immunoreactive cell numbers and density in the AVPV, MePO, and MPN were significantly higher in old compared with young or middle-aged rats. No change in the total number or density of ERalpha-immunoreactive cells was detected with age, although when cells were subdivided by intensity of immunolabeling, the most heavily labeled ERalpha cells increased in number with aging in the AVPV and MePO, and in density in the AVPV. There are several interpretations to our finding of substantially increased AR cell numbers during aging, including a potential compensatory upregulation of the AR under diminished testosterone concentrations. These results provide further information about how the neural targets of steroid hormones change with advancing age.