Chronic estradiol administration did not cause loss of hypothalamic LHRH or TIDA neurons in young or middle-aged C57BL/6J mice.

Age-related decline in estrous cycle frequency and impaired pre-ovulatory gonadotropin surges at mid-life are modelled in young C57BL/6J mice by chronic (3 months) oral administration of estradiol (E2). However, the cellular events that induce damage to the neuroendocrine center that regulate gonadotropins with age or following E2 treatment are unclear. To address this issue, possible neuron loss was examined in relation to the loss of estrous cyclicity in E2-treated mice, in particular neurons of the hypothalamic luteinizing hormone releasing hormone (LHRH) and/or tuberoinfundibular dopaminergic (TIDA) systems. By immunocytochemical methods, there was no change in the number of LHRH or TIDA neurons in mice that have become acyclic due to age or E2 treatment. We conclude that the onset of acyclicity at middle-age or following chronic E2 treatment is not associated with loss of LHRH or TIDA neurons and that other neuroendocrine changes must be considered for the cause of acyclicity, particularly those involved in the synaptic regulation of LHRH secretion.