α-MSH analogues and adrenal zona glomerulosa function

Recent studies on the control of adrenal zona glomerulosa function and aldosterone secretion have focussed attention on the role of MSH- like peptides. In particular, at low concentrations, α-MSH has a specific stimulatory effect on rat adrenal glomerulosa cells. The synthesis of α-MSH analogues which have potent and prolonged effects on melanocyte systems offers new methods of examining the specificity of this response. Two peptides were tested in which potential for a β-turn configuration was stabilised. These were: [Nle⁴, D-Phe⁷]-α-MSH and the cyclic [cys⁴, Cys¹⁰]-α-MSH. In contrast to their effects on molanocyte systems, only [cys⁴, Cys¹⁰]-α-MSH stimulated glomerulosa cells, and it was equipotent with a α-MSH, while [Nle⁴, D-Phe⁷]-α-MSH and shorter fragments had no effect when added alone [Nle⁴, D-Phe⁷]-α-MSH, however, augmented the response of cells already maximally stimulated with α-MSH and in this respect its actions resembled those of γ-MSH and related peptides. The augmentation produced by [Nle⁴, D-Phe⁷]-α-MSH and γ₃-MSH was not additive when the two peptides were added together with α-MSH. The results suggest that the specificity of the α-MSH receptors in rat adrenal glomerulosa cells and the peptide structure-function relationships in this system are different from those described for melanocytes.