Gonadal hormone dependent developmental plasticity of catecholamine:beta 2-adrenoceptor signaling complex in male rat thymus: Putative implications for thymopoiesis
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The study was undertaken considering that: i) androgens affect beta(2)-adrenoceptor (AR)-mediated catecholamine (CA) action in many tissues; and ii) peripubertal changes in both circulating androgen and thymic CA levels are implicated in rat thymic involution. Its aims were to: i) explore putative effects of the late prepubertal orchidectomy on thymic CA:beta(2)-AR complex in young adult rats, and ii) delineate the direct effects of testicular hormone withdrawal on the CA:beta(2)-AR complex from those elicited secondarily through altered influence of this complex components on each other's availability. Upon showing that prepubertal orchidectomy augmented the efficacy of thymopoiesis through increasing the thymocyte surface density of Thy-1, whose expression is negatively regulated by beta(2)-AR-mediated signaling, we examined the effects of orchidectomy and 14-day-long propranolol (PROP) treatment in orchidectomized (ORX) and sham-ORX rats on thymic norepinephrine (NE) concentration a...nd metabolism and beta(2)-AR expression. Orchidectomy, despite an increase in the average NE amount per thymocyte and total thymocyte NE content diminished thymic NE concentration. This decrease reflected the diminished density of CA-synthesizing nerve fibers, CD68 + macrophages, cortical (aminopeptidase A+), and medullary (UEA-1+) thymic epithelial cells (TECs) and their CA content (probably due to lessened TH expression accompanied by increased MAO-A expression). Moreover, orchidectomy decreased the surface beta(2)-AR expression on thymocytes, CD68+ macrophages and OX-62+ dendritic cells, but increased its expression on the TECs. In sham-ORX rats, PROP reduced thymic NE concentration by diminishing TH expression in the thymic cells. Additionally, PROP in thymocytes and thymic stromal cells diminished and enhanced the beta(2)-AR mRNA expression, respectively. However, in ORX rats PROP did not significantly affect CA(NE):beta(2)-AR complex components. This indicated that prepubertal orchidectomy affects ability of young adult rats to respond to beta-AR blockade by altering thymic NE and beta(2)-AR availability. Collectively, the results showed that testicular hormones contribute to alterations in thymus/thymopoiesis during the critical peripubertal period by shaping modulatory sympathetic influence and CA autocrine/paracrine action within the organ.
Ključne reči:Thymus / Sympathetic innervation / beta 2-Adrenoceptors / Orchidectomy / Catecholamine metabolizing enzymes
Izvor:Journal of Neuroimmunology, 2013, 265, 1-2, 20-35
- Elsevier Science BV, Amsterdam