Melanocyte-stimulating hormone (MSH)

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Melanocyte-stimulating hormone (MSH) and its derivatives

The melanocyte-stimulating hormone (MSH) is the body’s peptide hormone that regulates the function of skin pigment cells (melanocytes) [1]. MSH also affects other types of cells [2, 3] and different synthetic forms have been made from it [4] that are analogic to the body's MSH. Polypeptides that imitate the body's MSH include Melanotan I and Melanotan II (the so-called Barbie drug) that is sold illegally on the Internet.

MSH especially affects the skin functions. The skin structure is multi-layered [5]. The outermost layer of the skin, called the stratum corneum, is composed of dead and cornified cells. Under the stratum corneum is the epidermis. The innermost layer of the epidermis contains special pigment cells, melanocytes, that produce melanin and are regulated by MSH.

When skin is exposed to ultra-violet rays, melanin binds the rays to itself, and as a consequence of this, melanocytes are activated and start to produce more melanin [5]. When the amount of melanin increases, the color of skin became darker. The melanin pigment of the skin protects the skin against injuries caused by ultra-violet rays [2].

MHS is also found also to affect nutrient intake [6, 7]. If in the body has absorbed more nutrients than cells need at that moment, the extra is stored as a form of glycogen or fat tissue [5]. Between meals, the body releases energy from these reserves. The body hormonally regulates the release and storing of nutrients.

Medical use

MSH has many points of action, receptors, in the body that enable it to be used for many different medical uses [3]. The α-MSH analog (afamelanotide) was preliminarily researched, for example, for the treatment of the Erythropoietic Protoporphyria (EPP) [8]. The α-MSH analogs have also been studied for the treatment of erectile disorders.

Properties and mechanism of action

In research, it has been found that synthetic α-MSH increases skin pigmentation [9, 4]. The α-MSH has been found to significantly increase the amount of melanin in the skin while at the same time, skin injuries caused by UV-radiation decrease [4].

In addition to the pigmentation of the skin, MSH is found to have an effect on sexual functions and the regulation of nutrient intake. The α-melanocyte-stimulating hormone decreases the amount of ingested nutrients [6, 7], which can cause weight loss. The reported adverse effects of Melanotan II are nausea and decreased appetite, which may also explain the loss in weight that may possibly be connected with the use of melanocyte-stimulating hormones.


Synthetic α-MSH is used because of its skin-tanning effect. Also weight loss and increased libido are reasons for the use of α-MSH analogs. Thus, the Melanotan II preparation is also called the Barbie drug.

Adverse effects

In research on α-MSH analogs, several adverse effects are reported such as nausea and face reddening [9, 10, 4]. Adverse effects also include tiredness [10, 4] and vomiting [4]. When the effects of  synthetic α-MSH were researched, it was found that the hormone analog also causes spontaneous erections, pandiculation and yawning.

MSH and its analogs have many effects on the organism. When using MSH analogs, there is no assurance that only the wanted effects of the hormone will appears, but adverse effects may also appear.

This is due to the fact that the target receptors of MSH are in many parts of the organism. Injected MSH, or its synthetic analog, can affect all of these receptors and cause unwanted effects. In addition, the composition of the analogs purchased from Internet shops, such as the Melanotan II preparation, is not known. Therefore, the safety of its use is difficult to assess.

Salla Ruuska
M.Sc., Pharmacist

[1] Tirri, Lehtonen, Lemmetyinen, Pihakaski & Portin  (2001): Biologian sanakirja. Kustannusosakeyhtiö Otava, Keuruu.

[2] Thody & Graham (1998): Does α-MSH Have a Role in Regulating Skin Pigmentation in Humans? Pigment Cell Research 11:265-274.

[3] Bertolini, Tacchi & Vergoni (2009): Brain effects of melanocortins. Review. Pharmacological Research 59:13-47.

[4] Barnetso, Ooi, Zhuang, Halliday, Reid, Walker, Humphrey & Kleinig (2006): [Nle4-D-Phe7]-α-Melanocyte-Stimulating Hormone Significantly Increased Pigmentation and Decreased UV Damage in Fair-Skinned Caucasian Volunteers. Journal of Investigative Dermatology 126:1869-1878.

[5] Haug, Sand, Sjaastad & Toverud (1999): Ihmisen fysiologia, ss. 147-154, 323-327, 371-410, 411-422. WSOY, Porvoo.

[6] Smith (2000): The Controls of Eating: A Shift from Nutritional Homeostasis to Behavioral Neuroscience. Nutrition 16:814-820.

[7] WilliamS, Bing, Cai, Harrold, King & Liu (2001): The hypothalamus and the control of energy homeostasis. Different circuits, different purposes. Physiology & Behavior 74:683-701.

[8] Harms, Lautenschlager, Minder & Minder (2009): Mitigating Photosensitivity of Erythropoietic Protoporphyria Patients by an Agonistic Analog of α-Melanocyte Stimulating Hormone. Photochemistry and Photobiology 85:1434-1439.

[9] Dorr, Lines, Levine, Brooks, Xiang, Hruby & Hadley (1996): Evaluation of Melanotan-II, a Superpotent Cyclic Melanotropic Peptide in a Pilot Phase-I Clinical Study. Life Sciences 58:1777-1784.

[10] Dorr, Ertl, Levine, Brooks, Bangert, Powell, Humphrey & Alberts (2004): Effects of a Superpotent Melanotropic Peptide in Combination With Solar UV Radiation on Tanning of the Skin in Human Volunteers. Archives of Dermatology 140:827-835.

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