The thymus gland as a major target for the central nervous system and the neuroendocrine system: Neuroendocrine modulation of thymic beta(2)-Adrenergic receptor distribution as revealed by in vitro autoradiography.
The existence of a dense structural and hormonal innervation of the immune system provides the first link in the interaction among the central nervous system, the endocrine system and the immune system. Our recent localization of a specific beta(2)-adrenergic receptor population in the medulla of the rat thymus gland, undergoing important changes in density and distribution during ontogenic development, coupled with a marked sexual dimorphism during maturation, prompted us to study changes in distribution of the thymic beta-adrenergic receptor under experimental conditions accompanied by marked fluctuations of the sex steroid hormonal milieu, using in vitro autoradiography. Moreover, such changes were correlated with alterations in thymocyte proliferative response and thymus histology. Slidemounted cryostat sections were incubated with iodocyanopindolol ([(125)I]CYP), a specific ligand for beta-adrenergic receptors. Labeling was detected by autoradiography, by exposing the sections to Ultrofilm (LKB). The vast majority of receptors localized in the medullar compartment of the thymus are of the beta(2)-subtype, with no qualitative changes in the predominant beta(2)-adrenergic population under the different conditions studied. During the rat estrous cycle, a significant increase in density of the receptor was observed on proestrous, compared to the other phases of the cycle. Castration produced a marked decrease in density and loss of organization of the receptor in the medulla, coupled with a marked hypertrophy of the cortical region and a significant increase in cell-mediated immune response. On the other hand, treatment with estradiol, alone or in combination with progesterone, resulted in a profound stimulation of beta-adrenergic receptor density, together with an inhibition of thymus weight, atrophy of the cortex, and reduced thymic proliferative capacity. Present results indicate that the thymic beta-adrenergic receptor is dramatically influenced by the sex steroid hormonal milieu and that estrogen is a potent stimulator of receptor density. It is suggested that the steroidal modulation of the beta(2)-adrenergic receptor may play a role in the changes of sensitivity of the thymic cells to the changing repertoire of the thymic microenvironment, indicating that this receptor population is involved in a neuroendocrine-immune regulatory loop, thereby providing a functional integration of neural, immune, and endocrine signals.
Marchetti
B
B
Department of Pharmacology, Medical School, University of Catania, 95125 Catania, Italy.
Morale
M C
MC
Pelletier
G
G