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ACTH1-4 potentiates alpha-MSH-induced melanophore dispersion and excessive grooming
Abstract:
The biological activity and a possible modulatory role of the N-terminal tetrapeptide Ser-Tyr-Ser-Met from alpha-MSH/ACTH was tested in the Anolis melanophore assay, the Xenopus melanophore assay, tyrosinase stimulation in mouse melanoma cells and in excessive grooming in the rat. ACTH1-4 did not exhibit biological activity in any of these four assays nor did it have modulatory properties in the Xenopus and the melanoma cell assay. However, in the Anolis assay ACTH1-4 potentiated pigment dispersion induced by alpha-MSH, alpha-MSH5-13 and ACTH1-24 by a factor of about 2. In the grooming assay ACTH1-4 potentiated the effects of alpha-MSH, alpha-MSH5-13, ACTH1-16 and ACTH5-16, but not those of ACTH1-24. Oxidized ACTH1-4 was without biological activity and potentiating properties in all four assays. This study shows that small fragments of the pro-opiomelanocortin precursor, which are devoid of biological activity, can modulate peripheral and central actions of alpha-MSH/ACTH.
Insights
The N-terminal tetrapeptide Ser-Tyr-Ser-Met (ACTH1-4) from alpha-melanocyte-stimulating hormone/adrenocorticotropic hormone (alpha-MSH/ACTH) showed no direct biological activity. However, ACTH1-4 modulated pigment dispersion and grooming behaviors.
Area of Science:
- Endocrinology
- Neuroendocrinology
- Molecular Biology
Background:
- The pro-opiomelanocortin (POMC) precursor yields various bioactive peptides, including alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH).
- The biological roles of smaller POMC fragments are not fully elucidated.
Purpose of the Study:
- To investigate the biological activity and modulatory potential of the N-terminal tetrapeptide (Ser-Tyr-Ser-Met, ACTH1-4) derived from alpha-MSH/ACTH.
- To assess ACTH1-4's effects on peripheral and central functions.
Main Methods:
- Anolis and Xenopus melanophore assays for pigment dispersion.
- Tyrosinase stimulation assay in mouse melanoma cells.
- Excessive grooming assay in rats.
- Testing of oxidized ACTH1-4.
Main Results:
- ACTH1-4 lacked intrinsic biological activity in all tested assays.
- ACTH1-4 potentiated alpha-MSH-induced pigment dispersion in Anolis melanophores.
- ACTH1-4 modulated grooming behavior in rats, potentiating effects of certain alpha-MSH and ACTH fragments.
- Oxidized ACTH1-4 showed no activity or modulatory properties.
Conclusions:
- Small, biologically inactive fragments of POMC, such as ACTH1-4, can modulate the peripheral and central actions of alpha-MSH and ACTH.
- This suggests a complex regulatory network involving POMC-derived peptides.