Formation and Release of a Hormone Antagonist by Rat Adipocytes

A hormone antagonist that inhibits the ability of lipolytic hormone to increase adenosine cyclic 3',5'-monophosphate-(cAMP) levels has been found in isolated fat cells from epididymal adipose tissue of rats. Epinephrine, ACTH, or glucagon promoted the formation of this antagonist and its release into the incubation medium. The activity appearing in the medium was dependent on the time of incubation. An increase in the cAMP level in response to the hormone preceded the formation of the hormone antagonist, and the antagonist accumulated during the period when cAMP was decreasing toward the basal level. Both cAMP and dibutyryl-cAMP can mimic the action of hormones to promote the formation of antagonist. The antagonist formed by fat cells incubated with lipolytic hormone prevented the action of a second addition of the hormone, but the sensitivity to hormones could be restored by washing the cells with new medium. The material that accumulated following epinephrine stimulation prevented the action not only of epinephrine but also of ACTH or glucagon. The antagonist was partially purified. Its activity was not mimicked by palmitate (1.0 m m ) or oleate (1.5 m m ). The inhibitory activity in the incubation medium was equivalent to nanomolar quantities of prostaglandin E 1 , but the partially purified antagonist, unlike prostaglandin E 1 , did not elevate cAMP in human platelets or rat spleen slices. The antagonist may be involved in a negative feed back loop-moderating hormone response.