Peripubertal ovariectomy influences thymic adrenergic network plasticity in adult rats

• Published in: Journal of neuroimmunology 2016-08, Vol.297, p.103-116
• Main Authors: Pilipović, Ivan, Vujnović, Ivana, Arsenović-Ranin, Nevena, Dimitrijević, Mirjana, Kosec, Duško, Stojić-Vukanić, Zorica, Leposavić, Gordana
• Format: Article
• Language: English
• Subjects: Age Factors; Allergy and Immunology; Animals; Cell Proliferation; Chromatography, High Pressure Liquid; Estradiol - blood; Female; Flow Cytometry; G-Protein-Coupled Receptor Kinase 3 - genetics; G-Protein-Coupled Receptor Kinase 3 - metabolism; Gene Expression Regulation - physiology; Nerve Net - metabolism; Neurology; Noradrenaline; Norepinephrine - metabolism; Ovariectomy; Peripubertal ovariectomy; Progesterone - blood; Rats; Receptors, Estrogen - genetics; Receptors, Estrogen - metabolism; RNA, Messenger - metabolism; Thymocytes - metabolism; Thymus; Thymus Gland - cytology; Tyrosine 3-Monooxygenase - genetics; Tyrosine 3-Monooxygenase - metabolism; α1-Adrenoceptors; β2-Adrenoceptors
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2016.05.017

Abstract The study investigated the influence of peripubertal ovariectomy on the thymic noradrenaline (NA) concentration, and the thymocyte NA content and β2 - and α1 -adrenoceptor (AR) expression in adult 2- and 11-month-old rats . In control rats, the thymic NA concentration increased with age. This increase reflected rise in the density of catecholamine (CA)-containing fluorescent nerve fibers and cells and their CA content. Additionally, the average β2 - and α1 -AR thymocyte surface density changed in the opposite direction with age; the density of β2 -AR decreased, whereas that of α1 -AR increased. Ovariectomy diminished the thymic NA concentration in 2-month-old rats. This reflected the decrease in the density of fluorescent nerve fibers, and CA content in fluorescent nerve fibers and non-lymphoid cells, since the thymocyte NA content was increased in ovariectomized (Ox) rats. Estrogen supplementation prevented the ovariectomy-induced changes. In Ox rats, the density of CA- synthesizing nerve fibers and non-lymphoid cells diminished with age. To the contrary, NA content in thymocytes increased with age, but it did not exceed that in 11-month-old controls. Additionally, ovariectomy diminished the average thymocyte surface density of β2 -ARs, but it increased that of α1 -ARs in 2-month-old-rats (due to estrogen, and estrogen and progesterone deficiency, respectively). These changes, despite of the rise in circulating estrogen level post-ovariectomy, remained stable with age. This most likely reflected a decreased sensitivity to estrogen action, as a consequence of the hormone misprinting in peripubertal age. The analysis of thymocyte proliferation in culture suggested that age- and ovariectomy-induced alterations in thymocyte NA synthesis and AR expression altered NA autocrine/paracrine action on thymocytes. In conclusion, the study indicates that the ovarian hormone deficiency in peripubertal age affects ovarian steroid-dependent remodeling of thymic adrenergic regulatory network in adult rats.