Neonatal androgenization affects the efficiency of beta-adrenoceptor-mediated modulation of thymopoiesis

Abstract

We tested the hypothesis that neonatal androgenization affects the efficacy of beta-adrenoceptor (beta-AR)-mediated fine tuning of thymopoiesis in adult female rats by modulating the thymic noradrenaline (NA) level and/or beta-AR expression. In adult rats administered with 1000 mu g testosterone enanthate at postnatal day 2 a higher density of catecholamine (CA)-synthesizing thymic cells, including thymocytes, and a rise in their CA content was found. In addition, in these animals increased thymic noradrenergic nerve fiber fluorescence intensity, reflecting their increased CA content, was detected. These changes were followed by an increase in thymic NA concentration. The rise in thymic NA content in thymic nerve fibers and cells was associated with changes in the expression of mRNA for enzymes controling pivotal steps in NA biosynthesis (tyrosine hydroxylase, dopamine-beta-hydroxylase) and inactivation (monoamine oxidase). In contrast, the thymic level of beta(2)-AR mRNA on a per cell basis and the receptor surface density on thymocytes was reduced in testosterone-treated (TT) rats. As a consequence, 14-day-long treatment with propranolol, a beta-AR blocker, was ineffective in modulating T-cell differentiation/maturation in TT rats. In conclusion, the study indicates the importance of the neonatal sex steroid milieu for shaping the immunomodulatory capacity of the thymic NA/beta-AR signaling system in adult rats.