Regulation of beta(1)- and beta(3)-adrenergic agonist-stimulated lipolyticresponse in hyperthyroid and hypothyroid rat white adipocytes

1 This study examined the effects of thyroid status on the lipolytic respon ses of rat white adipocytes to beta-adrenoceptor (beta-AR) stimulation. The beta(1)- and beta(3)-AR mRNAs and proteins were measured by Northern and s aturation analyses, respectively. Glycerol production and adenyl cyclase (A C) activity induced by various non-selective and selective beta(1)/beta(3)- AR agonists and drugs which act distal to the receptor in the signalling ca scade were measured in cells from untreated, triiodothyronine (T-3)-treated and thyroidectomized rats. 2 The beta(3)-AR density was enhanced (72%) by T-3-treatment and reduced (5 0%) by introduction of a hypothyroid state while beta(1)-AR number remained unaffected. The beta(1)- and beta(3)-AR density was correlated with the sp ecific mRNA level in all thyroid status. 3 The lipolytic responses to isoprenaline, noradrenaline (beta(1)/beta(3)/b eta(3)-AR agonists) and BRL 37344 (beta(3)-AR agonist) were potentiated by 48, 58 and 48%, respectively in hyperthyroidism and reduced by about 80% in hypothyroidism. 4 T-3-treatment increased the maximal lipolytic response to the partial bet a(3)-AR (CGP 12177) and beta(1)-AR (xamoterol) agonists by 234 and 260%, re spectively, increasing their efficacy (intrinsic activity: 0.95 versus 0.43 and 1.02 versus 0.42). The maximal AC response to these agonists was incre ased by 84 and 58%, respectively, without changing their efficacy. 5 In the hypothyroid state, the maximal lipolytic and AC responses were dec reased with CGP (0.17 +/- 0.03 versus 0.41 +/- 0.08 mu mol glycerol/10(6) a dipocytes; 0.048 +/- 0.005 versus 0.114 +/- 0.006 pmol cyclic AMP min(-1) m g(-1)) but not changed with xamoterol. 6 The changes in lipolytic responses to postreceptor-acting agents (forskol in, enprofylline and dibutenyl cyclic AMP, (Bu)(2)cAMP) suggest the modific ations on receptor coupling and phosphodiesterase levels in both thyroid st ates. 7 Thyroid status affects lipolysis by modifying beta(3)-AR density and post receptor events without changes in the beta(1)-AR functionality.