Adenyl Cyclase in Fat Cells

Among several lipolytic hormones tested, adrenocorticotropin (ACTH), epinephrine, glucagon, thyroid-stimulating hormone, and luteinizing hormone stimulated adenyl cyclase activity in a plasma membrane-rich fraction, termed “ghosts,” isolated from rat fat cells. The effects given by various combinations of these hormones, at maximally stimulating concentrations, were not additive, indicating that a single enzyme was activated by all of these hormones. Different effects of the combined hormones were found depending upon the condition of incubation. At 3’7”, the combined hormones either did not give greater effects or gave smaller effects than that of the most effective hormone. At 30” in the presence of an ATP-regenerating system, each hormone potentiated the effect of the other. The effects on adenyl cyclase activity of combinations of the hormones at concentrations near their apparent Km of activation displayed noncompetitive kinetics. Propranolol, a p receptor antagonist, blocked completely the stimulatory action of epinephrine but did not alter the actions of the peptide hormones. An analogue of ACTH inhibited, specifically and competitively, the stimulatory actions of ACTH both on adenyl cyclase activity in ghosts and on lipolysis in intact fat cells. It was concluded from these findings that the hormones act at discrete hormone-specific sites (or receptors) that affect the activity of a single adenyl adenyl cyclase in fat cells.