Polyamines: a new opportunity in baldness therapy


Polyamines and their application in the therapy of baldness

The continuous search for new products able to provide a contribution to the treatment of baldness, leads us to evaluate the action of Polyamines, substances with well-known trichological properties, in relation to the action of Potassium Channels, whose existence within the Follicle Piliferous has recently been demonstrated and whose operativity has been evaluated.

What are the Polyamines

Polyamines are organic compounds consisting of two or more amine groups.

Their laboratory synthesis and the discovery of their chemical structure dates back to 1924 thanks to Rosenheim’s studies, although, thanks to the first microscopic observations, it was Van Leeuvenhoen, at the beginning of the 17th century, who detected the presence of crystalline compounds in human seminal fluid.

Polyamines are multifunctional cationic amines and, as such, are key substances in the cell proliferation cycle.

The most common polyamines (spermidine, spermine, putrescein, cadaverine) play a regulatory role in the cell cycle and have a fundamental function in the supercoiling of DNA chains in the cell nucleus.

In particular, rapidly proliferating tissues, contained in organs such as the Piliferous Follicle, need the synthesis of polyamines for an efficient cell cycle.

How polyamines act

A study conducted by the Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel, has provided valuable scientific evidence for the role of Polyamines as potent stimulators of hair growth and as modulators of human epithelial stem cells.

The effects of Polyamines on hair follicles and human hair follicle epithelial stem cells were studied in serum-free organic cultures.

Under these conditions, Polyamines caused sensitive elongation of the hair shaft and promoted prolongation of the Anagen phase..

Polyamines were also shown to over-regulate keratin expression by epithelial stem cells.

Interactions between polyamines and certain ion channels are also evident:

A study conducted by K. Williams, of the Faculty of Pharmacy at the University of Pennsylvania, showed a marked modulation of some channel receptors, in particular of Potassium K(+), and on some receptors of Glutamate by Polyamines.





Fallout on the hair follicle of interactions between polyamines and Potassium K(+)

Potassium K(+) channels play an important role in the regulation of the cell cycle, although less recognized than that of Polyamines; these channels, in fact, play a crucial role in the modulation of the electric field (hyperpolarization or depolarization of the membrane.

The interaction between polyamines and K+ channels is of great importance, since the modulation of the chemical level operated by polyamines, affects the electrical potential of some channels, including those of potassium, and this in turn has a significant influence on the regulation of the membrane potential during the cell cycle.

In fact, the unlocking of potassium channels is the cause of hyperpolarization, which allows electrochemical forces to move.

Conversely, blockage of K(+) channels can cause depolarization, resulting in blockage of the passage of Potassium across the cell membrane.

It is therefore evident that both an arrest of polyamine synthesis and a blockage of Potassium K(+)channels can arrest or strongly inhibit the cell proliferation cycle, with a negative effect on the hair cycle as well.

Experimentally it has been demonstrated that Ornithine, a well-known blocker of K(+) channels, decreases the concentration of Polyamines, with a blocking effect on the enzyme Ornithine Decarboxylase (ODC) and a consequent inhibition of the cell proliferation cycle.

It is therefore evident the essential function performed by K(+) channels in allowing polyamines to perform their function correctly, with important effects on the cell cycle, including those of the hair follicle (HF).




Potassium Channels, Follicles Piliferous (HF) and their reactivity to Minoxidil

Despite the widespread and established use of Minoxidil as a therapy for baldness, its mechanism of operation has not yet been fully clarified, the most accepted theories refer to an action on the vascularization of the hair bulb and an effect on the cells of the follicle.

To better clarify the mechanism of operation, it has been experimentally demonstrated that some drugs such as Minoxidil, and the Diazoxide stimulate the growth of hair follicles in vitro through a mechanism involving the ATP-sensitive potassium channels (K (ATP)), while substances blocking the same channels, such as Tolbutamide and Glibenclamide block it..

To demonstrate the mechanism of operation, the following has also been demonstrated.

  • that K(ATP) channels are present within hair follicles (HF),
  • that they reside in different parts of the follicle and that they react differently to each other when stimulated by Minoxidil

We used both Minoxidil, whose properties are known in the trichological field, and Tolbutamide, a substance known as a blocker of K channels (ATP); following the use of these substances, we evaluated the contrasting effects on the Anagen phase of follicles (HF) grown in vitro, with and without insulin.

The results obtained record a marked reactivity to both stimulating substances such as Minoxidil and inhibiting substances such as Tolbutamide, with relevant effects on the anagen phase, demonstrating the existence and the active involvement of K(ATP) channels in the mechanism of operation of Minoxidil within hair follicles..

Furthermore, a reverse transcriptase-polymerase chain reaction identified within the follicle (HF) the characteristic gene expression of the two components of potassium K(ATP) channels, subdivided into its main components the characteristic structure:

SUR sulfonylurea receptors (SUR 1 and SUR 2A), and the K(+) regulators Kir.6x (Kir 6.1 and Kir 6.2)

More specifically, at the epithelial matrix level, Kir 6.2 /SUR1 channels were found, whereas at the dermal papilla level, Kir 6.1/SUR2B channels were detected.

These results indicate not only thathuman follicles (HF) respond to potassium K(ATP) channel regulators, but that within human follicles some of the characteristic elements of the structure of these channels are expressed.

It is also confirmed that K(ATP) channels respond well to Minoxidil, through a positive action on the Anagen phase, which is significantly prolonged.

The study in question, however, has also shown that Minoxidil acts only on SUR2B receptors, present only in the Dermal Papilla, while SUR1 receptors, present in the Matrix, do not react to the administration of Minoxidil.






Development opportunities for Trichology

These results represent a valid development prospect for new drugs acting via SUR1 K(ATP) channels, which were found in Matrix cells..

The use of these drugs in the context of therapies that already provide for the use of minoxidil, which acts through SUR2B channels, would be of great interest for the therapy of baldness, since these drugs would go to act, in a coordinated manner, on different parts of the hair follicle, with a combined effect never experienced in the past..

It has been demonstrated that follicles respond biologically in culture to Katp potassium channel regulators, which express genes and proteins for 2 types of channels (SUR 1 and SUR 2B receptors and Kir6.2/SUR1 and Kir6.1/SUR2 pore-forming units); thus, it emerges that the dermal papilla contains Katp channels, as evidenced by the reactivity to stimulants such as Minoxidil, and inhibitors such as Tolbutamide.

The fact that Minoxidil stimulates only SUR2 channels opens up interesting development scenarios for scientific and pharmacological research.

It is therefore worth to follow very carefully the developments in this direction, since the enhancement through a synergistic action of polyamines with other specific drugs, can lead to important results in the therapy of baldness.


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