Characterization, expression, and hormonal control of a thymic beta 2-adrenergic receptor.
In the present study, we have characterized the beta 2-adrenergic receptor (beta 2-AR)-adenosine 3',5'-cyclic monophosphate (cAMP) system of the rat thymus gland and examined the hormonal regulation of the thymic beta 2-AR gene expression under physiological or pharmacological conditions accompanied by marked alterations of the sex steroid hormone milieu. We report here that membrane preparations of female rat thymic tissue contain iodocyanopindolol binding sites that exhibit pharmacological properties typical of a beta-AR. Detailed analysis by computer 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 radioligand binding studies was corroborated functionally by the rank order of potencies of a series of adrenergic agonists to stimulate the production 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. Physiological regulation of specific beta 2-AR in the rat thymus was indicated by significant increases in both receptor concentration and steady-state levels of beta 2-AR mRNA during the diestrous 2 and proestrous phases of the rat estrous cycle and pregnancy, whereas castration sharply reduced beta 2-AR numbers and transcript levels within the thymus. The modulation of the thymic beta 2-AR-cAMP signaling system by the preexisting sex steroid milieu, coupled with the sex-dependent adrenergic modulation of thymic cell-mediated immune response, may contribute to the various sex-related alterations in immune responsiveness and could play a role in sexually related immune disorders.
Department of Pharmacology, Medical School, University of Catania, Italy.
B
B
Marchetti
M C
MC
Morale
P
P
Paradis
M
M
Bouvier
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002455:Cell Division; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D006150:Guanine Nucleotides / Q000494:pharmacology; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012727:Sex Characteristics; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*
D012739:Gonadal Steroid Hormones; D006150:Guanine Nucleotides; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D000262:Adenylyl Cyclases