Steroidogenic activity of highly potent melanotropic peptides in the adrenal cortex of the rat.

Highly purified ACTH and MSH peptides were studied in isolated rat glomerulosa and inner zone cells and their activity compared with that in an Anolis melanophore assay. While both ACTH1-39 and ACTH1-24 were almost equally potent steroidogenic peptides in the two cell types (ED50 between 1 and 4 X 10(-12) M), alpha-MSH displayed only weak steroidogenic activity. Although it was a full agonist, it was about 10(4)-fold less potent in both capsular and inner zone cells. beta-MSH (porcine) was even 10-fold less active in capsular cells than alpha-MSH, and in inner zone cells it was a partial agonist. Highly potent melanotropic peptides, such as (Nle4, D-Phe7)-alpha-MSH or cyclic (Cys4, Cys10)-alpha-MSH were either inactive or exhibited only a very slight partial steroidogenic activity in both cell types. Comparison of the activity profile of additional compounds, such as des-acetyl alpha-MSH, (Tyr(I)2)-alpha-MSH, (Trp(For)9)-alpha-MSH or (Nva12)-alpha-MSH, in the adrenocortical and pigment cell assays led to the conclusion that alpha-MSH does not exert its steroidogenic effect through a typical melanocyte-type of MSH receptor, but rather through a low affinity-type of ACTH receptor.