Estrogen differentially regulates the expression of tyrosine hydroxylase and nerve growth factor through free radical generation in the thymus and mesenteric lymph nodes of middle‐aged ovariectomized female Sprague–Dawley rats

Objective Sympathetic neuronal activity in the thymus and lymph nodes is differentially regulated during reproductive aging. The aim was to investigate the role of estrogen on sympathetic neuronal expression in the thymus and mesenteric lymph nodes of early middle‐aged ovariectomized female rats implanted with 17β‐estradiol pellets. Methods 17β‐Estradiol pellets (0.6 and 300) were implanted subcutaneously in ovariectomized middle‐aged female Sprague–Dawley rats (n = 8/group) for a period of 30 days. At the end of the treatment period, the thymus and mesenteric lymph nodes were isolated and analyzed for the expression of tyrosine hydroxylase, nerve growth factor, and p‐ERK, p‐CREB and p‐Akt. Results The age‐related increase in tyrosine hydroxylase expression in the thymus was abrogated by ovariectomy, while estrogen suppressed it further and nerve growth factor expression was altered based on the dose of estrogen. In contrast, estrogen increased tyrosine hydroxylase and nerve growth factor expression in the mesenteric lymph nodes. Estrogen enhanced p‐ERK/total ERK, CREB/total CREB and p‐Akt/total Akt expression in a dose‐dependent manner. Free radical generation was augmented by estrogen in the thymus alone. Conclusions These results suggest that estrogen differentially influences sympathetic neuronal activity in the primary and secondary lymphoid organs to influence immunity. Estrogen reduced thymic p‐TH expression while low dose of estrogen alone increased NGF expression in thymus. Estrogen upregulated p‐TH and NGF expression in Mesenteric Lymph Nodes (MLN). Both doses of estrogen increased lipid peroxidation and ROS production in thymus.