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PT-141 Peptide: Potential in Melanocortin Studies

The natural hormone alpha-melanocyte stimulating hormone (α-MSH) is significantly altered to become PT-141. Simply put, PT-141 has been hypothesized to enhance libido by acting directly on the central nervous system. Some of the qualities of α-MSH are imitated, but not all. To better grasp how PT-141 functions, one must be familiar with the melanocortin system and the peptides that interact with it.

A Melanocortin: What Is It?

Understanding the melanocortin system is crucial to comprehending the mechanism of action of PT-141. Peptide hormones, or proteins composed of amino acids, are what all melanocortins are. The group’s name comes from the parent molecule from which all other melanocortins are produced: proopiomelanocortin (POMC). In the pituitary gland—a region of the brain that regulates development, sleep/wake cycles, libido, appetite, and other vital functions—POMC is produced. Adrenocorticotropic hormone (ACTH) and melanocyte-stimulating hormone (MSH) are two examples of natural melanocortins derived from polyoxymethylene chloride (POMC). 

Potential Impacts of Melanocortin

Unfortunately, a figure doesn’t adequately depict the diverse range of impacts that melanocortins may have. The fact is that it’s not possible to put all of these systems’ impacts onto a single graphic since they are so different. Despite the low production volume of melanocortin, many downstream processes are regulated by the local concentration and distribution of melanocortin receptors. Studies suggest melanocortin signaling may have a significant impact on many parts of biology, such as:

  • Pigmentation;
  • Cell Aging;
  • Muscle Cell Proliferation;
  • Reproductive Maturation
  • Obesity and Fat Cell Mass;
  • Insulin Intolerance;
  • Libido and Bonding Behaviors;
  • Pain Perception;
  • Caloric Intake

Melanocortin Receptors

Five distinct melanocortin receptors are considered to be present. When these receptors bind to melanocortin, the hormone impacts the organism. Melanocortins’ final effects depend on the exact site and binding pattern. Instead of “#,” the melanocortin receptors are abbreviated as “MC#R” and assigned a value between 1 and 5. Following is a list of the many locations where each MCR may be found.

  • MC1R- Melanocytes are the cells responsible for controlling pigmentation and are the primary sites of MC1R. Brain gray matter, astrocytes, leukocytes, and the kidney all contain it to a lesser extent. 
  • MC2R can be found in the kidneys, certain immune cells, and white fat. Its potential anti-inflammatory effects are secondary to its effect on fat metabolism.
  • MC3R—MC3R regulates intrinsic drive, caloric intake, the pace of development, and the beginning of reproductive development; it is only present in the brain.
  • MC4R—MC4R is ubiquitous in the organism and specifically the central nervous system. The following behaviors are linked to it: sexual arousal, learning mechanisms, anxiety/depression, pair bonding, food seeking, reward centers, and obesity. There are more agonists and antagonists identified for it than any other.
  • Fat cell accumulation and hunger hormone signaling are likely all impacted by MC4R. Involvement in the leptin pathway seems to be its function.
  • MC5R- Skin cells, red blood cells, and adipose tissue cells are the main locations for the MC5R receptor. A key player in modulating the inflammatory response, it controls skin sebum (oil) production. It also plays a crucial role in maintaining a core temperature and is necessary for the maturation of red blood cells. Some animals’ sexual arousal and mating behaviors are influenced indirectly by MC5R because of its significant involvement in pheromone synthesis. Whether MC5R influences pheromone signaling is not yet known.

PT-141 Peptide and Female Species

Studies suggest that the melanocortin system may regulate various physiological activities. PT-141 is also known as Bremelanotide, is a synthetic melanocortin with modest selectivity. According to the research, all melanocortin receptors, except for MC2R, seem to bind to varied degrees. On the other hand, it has been hypothesized to primarily bind and activate MC3R and MC4R.

Whereas antagonists work by blocking receptors, agonists activate them. Although PT-141 is theorized to enhance sexual arousal by activating MC4R, this is just half the picture. When examining the MC4R features in detail, it seems that activating that receptor affects goal-oriented behavior, pair bonding, and sexual desire. To rephrase, it is very unlikely that PT-141 might only influence sexual arousal by telling the brain to prepare for copulation and increasing blood flow to the genitalia. Additionally, scientists speculate it is likely to enhance innate mating behavior. The latter impact, partly mediated by oxytocin, motivates monogamous animals to form bonds, engage in copulation, and help raise their young.

Research suggests that binding sites for PT-141 other than MC4R are considered while discussing its mechanism of action. While PT-141’s actions on MC4R provide a picture of how it might induce arousal, it’s important to remember that its binding at MC3R may play a role, albeit indirectly, in its sexual impacts as well.

Receptor MC3R is known as the energy rheostat. MC3R has been speculated to regulate the body’s total energy expenditure and serve as a mechanism for adjusting behavior in pursuit of certain goals. 

Buy PT-141 from Biotech Peptides if you are a researcher interested in further studying the peptide. 

References

[i] R. N. Lippert, K. L. J. Ellacott, and R. D. Cone, “Gender-Specific Roles for the Melanocortin-3 Receptor in the Regulation of the Mesolimbic Dopamine System in Mice,” Endocrinology, vol. 155, no. 5, pp. 1718–1727, May 2014, doi: 10.1210/en.2013-2049.

[ii] H. Wessells, J. E. Blevins, and T. W. Vanderah, “Melanocortinergic control of penile erection,” Peptides, vol. 26, no. 10, pp. 1972–1977, Oct. 2005, doi: 10.1016/j.peptides.2004.11.035.

[iii] M. Sandrock, A. Schulz, C. Merkwitz, T. Schöneberg, K. Spanel-Borowski, and A. Ricken, “Reduction in corpora lutea number in obese melanocortin-4-receptor-deficient mice,” Reprod. Biol. Endocrinol. RBE, vol. 7, p. 24, Mar. 2009.

[iv] R. C. Rosen, L. E. Diamond, D. C. Earle, A. M. Shadiack, and P. B. Molinoff, “Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT[1]141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra,” Int. J. Impot. Res., vol. 16, no. 2, pp. 135–142, Apr. 2004. [PubMed]

[v] H. Wessells, V. J. Hruby, J. Hackett, G. Han, P. Balse-Srinivasan, and T. W. Vanderah, “Ac-Nle[1]c[Asp-His-DPhe-Arg-Trp-Lys]-NH2 induces penile erection via brain and spinal melanocortin receptors,” Neuroscience, vol. 118, no. 3, pp. 755–762, 2003. [PubMed]

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