Effects of testosterone and estradiol on stress-induced adrenal and hippocampal weight changes in female rats

OBJECTIVE To examine the impact of circulating testosterone (T) and the T/Estradiol (T/Ediol) ratio on chronic stress-induced changes of adrenal and hippocampal weight during proestrus (PE) and estrus (E) in female rats. DESIGN Stress was composed of repeated vaginal smear screening (VSS) and measured by the emotional reactivity score (ERS). Adrenal and hippocampal weight and the T, Ediol and T/Ediol ratio were assessed in PE and E controls as well as 20 h after sham or left adrenalectomy performed on diestrus-2 (DE-2) and PE, respectively. T was measured in ovariectomized (OVX) rats treated with estradiol benzoate (EB) or vehicle (VEH) and in non-OVX EB-treated rats. RESULTS In OVX rats EB treatment increased adrenal weight and T levels. After separation of VEH- and EB-treated rats into the low and high T-range (below and above the mean, respectively), it was observed that higher T was accompanied by higher adrenal weight in EB-compared to VEH-treated rats only in the low T-range. Non-OVX EB-treated rats with high T had lower adrenal weight compared to low T. Cycling rats assigned to the high T-range presented higher T/Ediol ratio but similar ERS and Ediol levels compared to rats in the low T-range, and were characterized by reduced adrenal weight, higher hippocampal weight and prevalence of PE versus E. CONCLUSIONS High T and high T/Ediol ratios are prominent in PE compared to E and exert a protective effect on hippocampal neuronal degeneration after similar chronic stress through T-mediated lessening of stress response thus counteracting the stress-promoting effects of Ediol.