ADRENERGIC REGULATION OF LIPOLYSIS IN FAT-CELLS FROM HYPERTHYROID ANDHYPOTHYROID PATIENTS

The influence of thyroid hormones on the adrenergic regulation of lipo lysis was studied in isolated adipocytes removed from the gluteal regi on of hyper- and hypothyroid women and compared in adipocytes from eut hyroid normal women. Noradrenaline significantly enhanced lipolysis in hyperthyroid patients, whereas noradrenaline inhibited lipolysis in h ypothyroid patients compared to that in controls. Moreover, beta-adren ergic sensitivity and responsiveness were 10- and 2-fold increased, re spectively, in hyperthyroid patients. In hypothyroid patients, beta-ad renoceptor responsiveness was reduced by 50%, whereas beta-adrenergic sensitivity remained unchanged compared with that in controls. Further more, the alpha(2)-adrenergic and adenosine-induced antilipolytic effe cts were similar in all thyroid states. The lowered beta-adrenergic re sponsiveness seen in hypothyroidism could be mimicked by agents acting at the levels of phosphodiesterase (enprofylline), adenylate cyclase (forskolin) and protein kinase (dibutyryl cAMP). In hyperthyroidism, t he increased beta-adrenergic sensitivity and responsiveness were not s een when lipolysis was stimulated at the adenylate cyclase, phosphodie sterase, or protein kinase levels. There was no change in the numbers of adipocyte beta- and alpha(2)-adrenoceptors in hypothyroidism. Howev er, the number of beta-adrenergic binding sites was doubled, whereas t he fraction and affinities of isoprenaline high affinity sites remaine d unchanged in hyperthyroidism. Thus, the influence of thyroid hormone on catecholamine-stimulated lipolysis in man acts through different m echanisms when adipocytes are exposed to high or low levels of thyroid hormones. In hyperthyroidism, lipolysis adapts to increasing energy d emands through an increase in the beta-adrenoceptor number and, thus, a more effective coupling of the adenylate-cyclase complex. In hypothy roidism, the low lipolytic effect of catecholamines seems to be mainly due to an impairment at the protein kinase level or to the hormone-se nsitive lipase itself.