Thyroid hormone modulation of epinephrine-induced lipolysis in rat adipocytes: a possible role of calcium.
Adipocytes isolated from normal, hypothyroid, and hyperthyroid rats were characterized with respect to their lipolytic activity (assessed by glycerol release) and beta-adrenergic receptors (assessed by binding of (--) [3H]alprenolol). Fat cells from hypo- and hyperthyroid rats showed the same affinity (K = 1.4 X 10(10) M(-1) and binding capacity (N = 1.21 X 10(-13) mol/microgram DNA) toward alprenolol as those from normal animals. Adipocytes from hypothyroid rats were unresponsive to epinephrine in a concentration range of 0.1-10 micron, with moderate responses at higher concentrations; injection of T3 in hypothyroid rats restored lipolytic responsiveness of the adipocytes to normal levels. Quabain (1 mM) inhibited lipolytic responses to epinephrine by 40--45% in normal and hyperthyroid rats; the lipolytic increment due to the hyperthyroid state was uninfluenced by ouabain. The lipolytic refractoriness to epinephrine of hypothyroid adipocytes was restored to normal levels by theophylline (1 mM) or EGTA  (1 mM); the theophylline and EGTA effects were not additive, suggesting that they stimulated lipolysis via a common mechanism. Epinephrine-induced lipolysis in all groups was progressively inhibited by increasing concentrations of Ca2+ in the medium. The Ca ionophore, A23187, showed a concentration-dependent inhibitory action. Theophylline (1mM) almost completely overcame the inhibitory action of the ionophore; in the presence of lower concentrations of theophylline, the inhibitory effect of the ionophore was least in hypothyroid and greatest in hyperthyroid fat cells. The findings suggest that the differences in the lipolytic response to epinephrine observed in hyperthyroid, euthyroid, and hypothyroid adipocytes are not due to alterations in the number or affinity of beta-adrenergic receptors nor to a membrane mechanism that might show differential ouabain sensitivity, but may be related to altered cellular Ca2+ concentrations which may indirectly alter cellular phosphodiesterase activity.
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000526:Alprenolol / Q000378:metabolism; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D006980:Hyperthyroidism / Q000378:metabolism; D007037:Hypothyroidism / Q000378:metabolism; D007700:Kinetics; D008053:Lipid Mobilization / Q000187:drug effects*; D008297:Male; D011441:Propylthiouracil; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013961:Thyroid Gland / Q000502:physiology*; D014284:Triiodothyronine / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D014284:Triiodothyronine; D000001:Calcimycin; D011441:Propylthiouracil; D000526:Alprenolol; D002118:Calcium; D004837:Epinephrine