Beta-adrenoceptor mediated responses and subtypes of beta-adrenoceptors in cultured rat Sertoli cells.
Membrane particles from Sertoli cell cultures were examined for subtypes of beta-adrenoceptors with a radioligand binding technique using [125I]iodocyanopindolol and a beta 1-selective antagonist (Sandoz 204 545) or a beta 2-selective antagonist (ICI 118 551). Biphasic competition curves and modified Eddie-Hofstee plots revealed a relative distribution of approx. 80% beta 1-adrenoceptors and 20% beta 2-adrenoceptors. Only 45% of the adrenoceptor mediated stimulation of adenylyl cyclase activity was associated with beta 1-adrenoceptors, whereas the remaining 55% was mediated via beta 2-adrenoceptors. The subtype selective antagonists inhibited isoproterenol stimulated aromatization of testosterone to estradiol-17 beta in a concentration-dependent manner. Complete inhibition of beta 1-adrenoceptors resulted in a 45% reduction of estradiol-17 beta formation, whereas similar inhibition of beta 2-adrenoceptors resulted in only a 35% reduction. It is concluded that cAMP-dependent effects of beta-adrenergic agonists in Sertoli cells are mediated by activation of both beta 1- and beta 2-adrenoceptors. The discrepancy between the relative number of beta 1- and beta 2-adrenoceptors and their relative contribution to cAMP production and aromatization indicates that beta 2-adrenoceptors in Sertoli cells are more tightly coupled to the adenylyl cyclase system than beta 1-adrenoceptors. Furthermore, complete inhibition of either beta 1- or beta 2-adrenoceptors by subtype selective antagonists, demonstrates a substantial fraction of spareness between agonist activation of the adenylyl cyclase complex and aromatization.
Eikvar
L
L
Institute of Medical Biochemistry, Rikshospitalet, University of Oslo, Norway.
Bjørnerheim
R
R
Attramadal
H
H
Hansson
V
V
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000378:metabolism*; D012708:Sertoli Cells / Q000378:metabolism*
D011941:Receptors, Adrenergic; D000262:Adenylyl Cyclases