CHARACTERIZATION, EXPRESSION, AND HORMONAL-CONTROL OF A THYMIC BETA(2)-ADRENERGIC RECEPTOR

In the present study, we have characterized the beta(2)-adrenergic rec eptor (beta(2)-AR)-adenosine 3',5'-cyclic monphosphate (cAMP) system o f the rat thymus gland and examined the hormonal regulation of the thy mic beta(2)-AR gene expression under physiological or pharmacological conditions accompanied by marked alterations of the sex steroid hormon e milieu. We report here that membrane preparations of female rat thym ic tissue contain iodocyanopindolol binding sites that exhibit pharmac ological properties typical of a beta-AR. Detailed analysis by compute r modeling of the binding potencies of a large series of beta(1)- and beta(2)-adrenergic agonists and antagonists revealed predominantly the beta(2)-AR subtype (78%) in rat thymus. This inference from radioliga nd binding studies was corroborated functionally by the rank order of potencies of a series of adrenergic agonists to stimulate the producti on of cAMP. Northern blot analysis, using a human beta(2)-AR cDNA as a probe, revealed the presence of a mRNA of 2.3 kb, which is consistent with the size of the beta(2)-AR mRNA found in other rat tissues. Phys iological regulation of specific beta(2)-AR in the rat thymus was indi cated by significant increases in both receptor concentration and stea dy-state levels of beta(2)-AR mRNA during the diestrous 2 and proestro us phases of the rat estrous cycle and pregnancy, whereas castration s harply reduced beta(2)-AR numbers and transcript levels within the thy mus. The modulation of the thymic beta(2)-AR-cAMP signaling system by the preexisting sex steroid milieu, coupled with the sex-dependent adr energic modulation of thymic cell-mediated immune response, may contri bute to the various sex-related alterations in immune responsiveness a nd could play a role in sexually related immune disorders.