Differential expression of estrogen receptor α and β immunoreactivity in the human supraoptic nucleus in relation to sex and aging

The dorsolateral supraoptic nucleus (dl-SON) is the main production site of plasma arginine vasopressin (AVP). Plasma AVP levels and the activity of AVP neurons in humans are higher in males than in premenopausal females. On the other hand, an increased activity of AVP neurons becomes prominent in postmenopausal women who have strongly decreased estrogen levels. As estrogens are presumed to inhibit AVP production in a receptor-mediated way, we studied estrogen receptor (ER) alpha and beta immunoreactivity in the dl-SON. Hypothalami of 34 controls were subdivided into 4 groups within a 50-yr boundary (young men, young women, elderly men, and elderly women). The AVP part of the dl-SON of young women contained 50 times more neurons with ER beta nuclear staining than that in young men and 250 times more than that in elderly women. In addition, young women also showed more ER beta cytoplasmic staining than young men and elderly women. In contrast to the ER beta immunoreactivity, no differences were found in the number of ER alpha-positive neurons in the 4 groups, but the age and sex pattern of ER alpha staining was basically opposite that of ER beta. Significant correlations between the percentage of ER beta- and ER alpha-positive and -negative AVP neurons and age were found in women, but not in men. Our data demonstrate for the first time a strong decrease of ER beta and an increase of ER alpha immunoreactivity in AVP neurons of the dl-SON of postmenopausal women. Both receptor changes are proposed to participate in the activation of the AVP neurons in postmenopausal women.