Melanocyte-Stimulating Hormone (MSH) and MSH-Sequences

Introduction

α-melanocyte stimulating hormone (α-MSH) is a family member of endogenous neuropeptide-melanocortin, derived from proopiomelanocortin (POMC) and secreted from the brain and pituitary gland. Serum α-MSH may act as a protective biomarker for non-traumatic osteonecrosis of the femoral head (ONFH). Systematic application of α-MSH serving as an adjunctive therapy for treating non-traumatic ONFH deserves further investigation. γ-Melanocyte stimulating hormone (γ-MSH) is an endogenous agonist of the melanocortin 3-receptor (MC3R). Previous studies have shown that multiple melanocortin peptides are present in osteoblastic like cells, which indicate that α-MSH might have an effect on osteoblast cells to regulate bone development and maturation.

Mechanism of action

α-MSH exerts its function via its cell surface receptors, named melanocortin receptors. Melanocortin receptors are G-protein coupled receptors, including MC-1R, MC-2R, MC-3R, and MC-4R. MC-1R is specifically expressed in the majority of melanomas, a leading cause of death related to skin cancers. Recent studies have proven that α-MSH protects the damage from dexamethasone on osteoblast-mediated by melanocortin receptors. These findings indicate that, α-MSH most likely acts directly as osteoblast or other related progenitor cells to participate in bone development and metabolism. α-MSH activates MC1R downstream ERK1/2 signaling to promote osteogenic differentiation and mineralization of osteoblast cells.

Application of Melanocyte-Stimulating Hormone (MSH) and MSH-Sequences

Due to the natural derivation of α-MSH and its effect on osteoblast differentiation based on the present study, α-MSH may be a potential candidate for a new generation of anti-osteoporosis drugs. Meanwhile, MC1R may provide a good target for designing therapeutic agents. Besides, α-melanocyte-stimulating hormone (α-MSH) has been characterized as a novel angiogenesis inhibitor. Based on the α-melanocyte-stimulating hormone sequence, MC-1R-targeted peptides have been studied for melanoma imaging, predominately for use with single-photon emission computed tomography, with few attempts made for positron emission tomography (PET). Over the years, different classes of α-MSH derivatives were developed and have seen successful usage for melanoma imaging.

References

1. Lei Wang., Jian Cheng., Zhen Hua., Mingming Liu., Haiyan Xu., Yong Ma., Guicheng Huang., &Guoqing Mao. (2019). α-melanocyte stimulating hormone (α-MSH) promotes osteoblast differentiation of MC3T3-E1 cells. European Journal of Pharmacology, 844(5), 1-8.
2. Eerola K., Virtanen S., Vähätalo L., Ailanen L., Cai M., Hruby V., Savontaus M., &Savontaus E. (2018). Hypothalamic γ-melanocyte stimulating hormone gene delivery reduces fat mass in male mice. Journal of Endocrinology, 239(1), 19-31.
3. Zheng Mao., Gang Liu., Jing-Jie Chen., Dan Liu., Min-Peng Xu., Chang Zhao., Hai-Tao Yang., Yong-Bin Yue. (2017). Serum α-melanocyte-stimulating hormone may act as a protective biomarker for non-traumatic osteonecrosis of the femoral head. Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, 55(4):453-460.
4. Chengcheng Zhang., Zhengxing Zhang., Kuo-Shyan Lin., Joseph Lau., Jutta Zeisler., Nadine Colpo., David M. Perrin., & Francois Benard. (2018). Melanoma Imaging Using 18F-Labeled α-Melanocyte-Stimulating Hormone Derivatives with Positron Emission Tomography. Molecular pharmaceutics, 15, 2116−2122.