Polyamines and hair: a couple in search of perfection

Abstract

Polyamines (spermidine, putrescine and spermine) are multifunctional cationic amines that are indispensable for cellular proliferation; of key significance in the growth of rapidly regenerating tissues and tumors. Given that the hair follicle (HF) is one of the most highly proliferative organs in mammalian biology, it is not surprising that polyamines are crucial to HF growth. Indeed, growing (anagen) HFs show the highest activity of ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis, while inhibition of ODC, using eflornithine, results in a decreased rate of excessive facial hair growth in vivo and inhibits human scalp hair growth in organ culture. In sheep, manipulation of dietary intake of polyamines also results in altered wool growth. Polyamine-containing nutraceuticals have therefore been proposed as promoters of human hair growth. Recent progress in polyamine research, coupled with renewed interest in the role of polyamines in skin biology, encourages one to revisit their potential roles in HF biology and highlights the need for a systematic evaluation of their mechanisms of action and clinical applications in the treatment of hair disorders. The present viewpoint essay outlines the key frontiers in polyamine-related hair research and defines the major open questions. Moreover, it argues that a renaissance in polyamine research in hair biology, well beyond the inhibition of ODC activity in hirsutism therapy, is important for the development of novel therapeutic strategies for the manipulation of human hair growth. Such targets could include the manipulation of polyamine biosynthesis and the topical administration of selected polyamines, such as spermidine.

Regenerative Medicine and Hair Loss: How Hair Follicle Culture has Advanced our Understanding of Treatment Options for Androgenetic Alopecia

“…Spermidine is a compound within the polyamine pathway, known to be important in hair growth [60]. Polyamines are found at low levels in resting cells, but at high levels where there is metabolic activity or proliferation, such as in anagen hair follicles.…”

N1-methylspermidine, a stable spermidine analog, prolongs anagen and regulates epithelial stem cell functions in human hair follicles

“…Considering their importance for almost every cellular function, including proliferation and differentiation, the polyamines [spermidine (Spd), putrescine and spermine] have long been suspected to be instrumental for normal hair growth [17,19]. Indeed, inhibition of ornithine decarboxylase-based polyamine synthesis inhibits human hair growth, and is clinically used for treating excess facial hair [9].…”

“…However, natural polyamines are readily interconvertible, and are physiologically unstable because they can be quickly metabolized [7,8,17]. This is particularly relevant for hair research, since different polyamines may exert diverse effects on hair growth [17].…”

“…This is particularly relevant for hair research, since different polyamines may exert diverse effects on hair growth [17]. For example, high levels of putrescine, which is metabolized from Spd, can lead to hair loss in mice, which might be due to an intrafollicular putrescine-hairless (HR) negative regulatory loop [11].…”

Topical eflornithine hydrochloride improves the effectiveness of standard laser hair removal for treating pseudofolliculitis barbae: A randomized, double-blinded, placebo-controlled trial

“…6 Eflornithine hydrochloride acts by inhibiting ornithine decarboxylase, an enzyme involved in hair cell division. 7 As a result, the medication can reduce the growth of the active hair follicles. Based on these studies, there have been several anecdotal reports on the benefits of using eflornithine in treating patients with PFB.…”