High density lipoprotein influences the response of rat adrenocortical cells to λ₃-melanotropin

Gamma ₃-melanotropin (γ₃-MSH) exhibits a marked dose-dependent synergism with ACTH_1-24 on corticosterone production by cells isolated from the inner zones of the rat adrenal cortex. This phenomenon is demonstrated to best advantage when donor animals are killed after stress or pretreatment with ACTH. If adrenal cells are prepared from quiescent or hypophysectomized animals, the inclusion of high density lipoprotein (HDL) in the incubation medium is required for a significant γ₃-MSH response. Dibutyryl cAMP can successfully substitute for ACTH_1-24 in these incubations but rat low density lipoprotein does not reproduce the HDL effect. These data are consistent with our in vivo studies demonstrating that γ₃-MSH potentiation is a product of increased cholesterol mobilization within the adrenal cortex and suggest that in the rat, a significant source of the cholesteryl ester pool which is responsive to γ₃-MSH may derive from circulating HDL.