Melanocyte Stimulating Hormones

There are three main varieties of MSH:

• Alpha Melanocyte Stimulating Hormone (α-MSH)
• Beta Melanocyte Stimulating Hormone (β-MSH)
• Gamma Melanocyte Stimulating Hormone (γ-MSH)

The table shows their structure. All of them are formed by splitting a common precursor protein - proopiomelanocortin .

MSH stimulate the synthesis and secretion of melanins (melanogenesis) by cell melanocytes of the skin and hair, as well as the retinal pigment layer. Alpha-melanocyte-stimulating hormone has the strongest effect on pigmentation.

In many amphibians and reptiles, MSH causes darkening of the integument in the dark or on a dark substrate, stimulating the dispersion of melanin granules inside skin melanophore cells.

In people, elevated MSH levels also cause darkening of the skin. This occurs, for example, during pregnancy, as well as in Addison's disease , when along with an increase in the level of ACTH, the level of MSH increases. Differences in MSH levels are not the main cause of interracial differences in skin color. People with red hair and fair skin, unable to tan, have a mutation in the gene of one of the MSH receptors.

MSH receptors belong to the family of serpentine receptors associated with G-proteins. In mammals, there are five types of melanocortin receptors.

• Mc1r (MC1, Mc1r or melanocyte stimulating hormone receptor) is one of the main proteins that regulate skin and hair color. It functions on the surface of melanocytes that regulate mammalian melanogenesis. Under the influence of one of the proopiomelanocortin cleavage products (usually an alpha melanocyte stimulating hormone), MC1R initiates a complex signaling cascade that leads to the production of black or brown eumelanin. In most mammals, this signal can be altered by binding of another protein to MC1R. Agouti signal protein (Asip) inhibits the interaction of MC1R. with alpha-melanocyte-stimulating hormone, which results in the production of red or yellow pheomelanin. The pulsating nature of signal transmission using Agouti via MC1R. leads to the development of a characteristic agouti color (alternation of yellow and black stripes on the hair) in most mammals. In some species, Agouti secretion is not pulsating, it does not change in time, but depending on the body area. This is especially noticeable in horses whose legs, tail and mane are black and their bodies are reddish. The exception is human hair, the color of which Agouti protein does not affect.

• Mc2r - adrenocorticotropic hormone receptor (ACTH receptor, MC2) is a specialized adrenal cortex cell receptor and responds to ACTH. It is located in the cortical layer of the adrenal gland and stimulates the production of cortisol. The ACTH receptor uses cAMP as an intermediary.

• Mc3r is present on cells of various tissues except the adrenal cortex and melanocytes. Knockout mice have an increased fat mass, despite reduced food intake, which indicates the involvement of this receptor in the regulation of nutritional homeostasis.
• Mc4r also binds α-melanocyte stimulating hormone. In mice, MC4R has been shown to be involved in the regulation of eating behavior, metabolism, and sexual behavior.

In 1998, it was discovered that mutations in the MC4R gene are associated with hereditary obesity in humans. They appear in a heterozygous state, which indicates the autosomal dominant nature of inheritance. Other studies and observations have shown that these mutations have incomplete dominance and some degree of coding.

• Mc5r. Its gene is located on the 18th chromosome of the human genome. When transgenic mice had malfunctioning MC5R, they showed malfunctioning of external secretion glands, which led to a decrease in secretion of sebaceous glands.

• Mc1r