Testing the critical window of estradiol replacement on gene expression of vasopressin, oxytocin, and their receptors, in the hypothalamus of aging female rats

The current study tested the critical window hypothesis of menopause that postulates that the timing and duration of hormone treatment determine their potential outcomes. Our focus was genes in the rat hypothalamus involved in social and affiliative behaviors that change with aging and/or estradiol (Es): Avp, Avpr1a, Oxt, Oxtr, and Esr2 in the paraventricular nucleus (PVN) and supraoptic nucleus (SON). Rats were reproductively mature or aging adults, ovariectomized, given E-2 or vehicle treatment of different durations, with or without a post-ovariectomy delay. Our hypothesis was that age-related changes in gene expression are mitigated by E-2 treatments. Contrary to this, PVN Oxtr increased with E-2, and Avprl a increased with age. In the SON, Avprl a increased with age, Oxtr with age and timing, and Avp was altered by duration. Thus, chronological age and E-2 have independent actions on gene expression, with the critical window hypothesis supported by the observed timing and duration effects. (C) 2015 Elsevier Ireland Ltd. All rights reserved.