title: Gonadal hormone dependent developmental plasticity of catecholamine:β2-adrenoceptor signaling complex in male rat thymus: putative implications for thymopoiesis.
abstract: The study was undertaken considering that: i) androgens affect β2-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:β2-AR complex in young adult rats, and ii) delineate the direct effects of testicular hormone withdrawal on the CA:β2-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 β2-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 and metabolism and β2-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 β2-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 β2-AR mRNA expression, respectively. However, in ORX rats PROP did not significantly affect CA(NE):β2-AR complex components. This indicated that prepubertal orchidectomy affects ability of young adult rats to respond to β-AR blockade by altering thymic NE and β2-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.
authors.affiliation: Immunology Research Centre "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", 458 Vojvode Stepe, 11221 Belgrade, Serbia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Pilipović
authors.forename: Katarina
authors.initials: K
authors.lastname: Radojević
authors.forename: Duško
authors.initials: D
authors.lastname: Kosec
authors.forename: Milica Perišić
authors.initials: MP
authors.lastname: Nanut
authors.forename: Zorica
authors.initials: Z
authors.lastname: Stojić-Vukanić
authors.forename: Nevena
authors.initials: N
authors.lastname: Arsenović-Ranin
authors.forename: Gordana
authors.initials: G
authors.lastname: Leposavić
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D043384:Glutamyl Aminopeptidase / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D009919:Orchiectomy; D037121:Plant Lectins / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013735:Testicular Hormones / Q000378:metabolism*; D060168:Thymocytes / Q000187:drug effects / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D037121:Plant Lectins; D011943:Receptors, Adrenergic, beta; D013735:Testicular Hormones; C036850:Ulex europaeus lectins; D011433:Propranolol; D014446:Tyrosine 3-Monooxygenase; D043384:Glutamyl Aminopeptidase
keywords: Catecholamine metabolizing enzymes; Orchidectomy; Sympathetic innervation; Thymus; β(2)-Adrenoceptors