The response of adenylate cyclase to ACTH in adipocyte membranes of lean and obese mice.

The response of adenylate cyclase to ACTH was examined in adipocyte membranes of lean (+/+) and obese (ob/ob) mice. The data show that the enzyme is more responsive to ACTH in membranes from obese than from lean mice. This is in contrast with the lower responsiveness of adenylate cyclase to catecholamines in the tissue of the obese than the lean mouse. In the obese, adrenalectomy completely abolished the response of cyclase to ACTH and in the lean, corticosterone supplementation augmented the ACTH response. These results show that glucocorticoids play an important role in the activation of adipocyte adenylate cyclase by ACTH and that the heightened response in the obese mouse adipocyte is related to hypercorticoidism. The results further establish that neither the hypercorticoidism nor the hyperinsulinism of the obese mouse is responsible for the impaired response of the adipocyte membranes to catecholamines, since adrenalectomy which corrected both hormonal excesses did not restore the adenylate cyclase response to isoproterenol.