Melanocyte-stimulating Hormone: Function & Diseases

Melanocyte-stimulating hormone (MSH) represents a group of peptide hormones that, among other things, regulate the production of melanin in melanocytes. This function is controlled by melanocortin receptors. In the context of Addison’s disease, there is an increased concentration of MSH, which here leads to the bronze coloration of the skin.

What is melanocyte-stimulating hormone?

Melanocyte-stimulating hormones are peptide hormones that perform different functions. Among other things, they are responsible for the formation of melamine. To perform their tasks, they dock onto the so-called melanocortin receptors. The melanocortin receptors are G-protein coupled receptors. These are membrane-bound receptors that, with the help of GTP-binding proteins, conduct signals into the cell, where they stimulate the initiation of various reactions. The melanocyte-stimulating hormones, also known as melanotropins, consist of three different peptide hormones. These are the alpha- beta- and gamma-MSH. All three MSH are formed from the prohormone proopiomelanocortin (POMC) along with the hormone adrenocorticotropin (ACTH) and beta-endorphin. All MSH and ACTH dock onto the same melanocortin receptors MC1R, MC2R, MC3R, MC4R, and MC5R to exert their effects.

Function, action, and roles

The function of melanocyte-stimulating hormones includes stimulating melanocytes to produce melanin. Particularly in the presence of increased UV radiation from the sun, there is increased production of MSH to provide better sun protection by browning the skin. In addition to melanin production, MSH also control the fever response and stimulate the hunger center. To mediate these functions, MSH must couple to melanocortin receptors. The individual receptors each mediate their own functions. The melanocortin receptor 1 (MC1R) controls hair coloration and skin tanning. Melanocortin receptor 2 (MC2R) mediates the action of ACTH. Another melanocortin receptor, MC3R, is expressed in the brain, placenta, or intestinal tissue. It is not found in melanocytes or the adrenal cortex. This receptor, with the help of MSH, controls the lowering of fever response and food utilization, reducing body fat storage. MC4R is also expressed in the brain, placenta and intestinal tissues and, with the help of MSH, slightly raises body temperature while suppressing the fever response. In addition, the hunger response is suppressed, metabolic energy consumption is affected, and sexual desire is increased. Melanocyte-stimulating hormones are released when needed. They are firmly integrated into the regulatory circuit of the endocrine system. When there is a high demand for ACTH, a greater amount of alpha-MSH is also produced at the same time. ACTH controls the formation of glucocorticoid hormones. Thus, it responds to a higher demand for these hormones. At the same time, more MSH is also produced.

Formation, occurrence, properties, and optimal levels

Melanocyte-stimulating hormones are formed in the hypothalamus or the pituitary intermediate lobe. There, they are formed by the decay of the prohormone proopiomelanocortin (POMC). POMC initially gives rise to ACTH, gamma-MSH and beta-lipotropin. In the process, alpha-MSH can form from ACTH through a further cleavage of a peptide residue. Beta-lipotropin breaks down into gamma-lipoprotein and beta-endorphin. Finally, beta-MSH is then formed from gamma-lipotropin.

Diseases and disorders

As mentioned earlier, melanocyte-stimulating hormones, along with ACTH and beta-endorphin, are formed from the prohormone proopiomelanocortin, abbreviated as POMC. Proopiomelanocortin is composed of 267 amino acids. Since this hormone is a prohormone, it must be intact to be broken down into effective hormones. The coding gene for proopiomelanocortin is located on chromosome 3. There is a known clinical picture based on mutations of this gene. Affected individuals suffer from severe obesity and renal cortical insufficiency at an early age. They also have a red hair color. Due to the defective formation of MSH, they can no longer fulfill their functions properly. Due to the disturbance of the hunger center and the regulation of energy consumption, enormous obesity develops. In addition, the formation of melanin is also disturbed. This causes the red hair.Since the hormone ACTH is also missing, the adrenal cortex can no longer be optimally stimulated. Mutations at the individual receptors can also cause partial MSH functions to fail, as they can no longer dock to the corresponding receptor. In other hormone-related diseases, melanocyte-stimulating hormones play only a minor role. However, they can contribute to typical symptoms of these diseases. Particularly in the context of Addison’s disease, a symptom occurs that is indicative of the increased concentration of MSH. Addison’s disease is often characterized by a bronze discoloration of the skin. Here, melanin is increasingly formed, which is deposited in the skin. Normally, a brown discoloration of the skin is seen as a sign of health. In Addison’s disease, however, it has a serious basis. Addison’s disease is a serious hormonal disorder that often even leads to death from organ failure. For some reason, the adrenal cortex is destroyed in this disease. This may be due to autoimmune processes, injury to this area, or other causes. In any case, the glucocorticoids cortisol, aldosterone and the sex hormones can only be produced to a small extent. This results in the main symptoms of this disease. However, since the hormonal system is subject to a regulatory mechanism, the hypothalamus is stimulated to produce more ACTH. However, even the increased ACTH concentration can no longer stimulate the formation of glucocorticoids because the adrenal glands are destroyed. In addition to the increased formation of ACTH, melanocyte-stimulating hormones are also increased. Melanocytes are stimulated to produce more melanin.