Mode of Action

The mode of action of the retinoids has not been completely elucidated, but they have profound effects on differentiation, cell growth, and immune response. Retinoids are capable of regulating epithelial differentiation in the skin, mucous membranes, and mesenchymal tissues. They promote cell proliferation in normal epidermis but inhibit epidermal keratinocytes in psoriatic lesions. Sebaceous glands are significantly reduced in size (up to 90%), and sebum excretion is reduced by isotretinoin. In general, retinoids are reported to stimulate humeral and cellular immunity, although immune-inhibitory effects have also been described. They can boost antibody production, increasing T-helper cells but not natural killer cells. Anti-inflammatory effects include inhibition of motility of neutrophils and eosinophils and their migration into the dermis. Isotretinoin seems to inhibit nitric oxide and tumor necrosis factor a production by keratinocytes and to reduce inducible nitric oxide synthase messenger RNA levels. The discovery of specific cellular binding proteins and nuclear receptors for retinoids has deeply advanced our understanding of the diverse biological processes of retinoids. These observations have also highlighted the complexity of interactions between retinoids and other hormonal signaling molecules. There are two groups of cellular binding proteins, the cellular retinol binding proteins (CRBP I and II) and the cellular retinoic acid binding proteins (CRABP I and II). CRABP II is the predominant form in human skin, although CRABP I is also present at low levels.

Expression of CRABP II is up-regulated by topical application of retinoic acid. CRABP II serves as an early marker for retinoic action in the skin and may regulate the bioavailability of retinoids by reducing the free levels available to reach the nucleus. Cellular retinoic acid binding proteins act as transporters across cell membranes and mediate transfer to the nucleus. In the nucleus of the target cell, retinoid molecules bind to their nuclear receptors. Two main classes of nuclear retinoid receptors have been identified, retinoic acid receptors (RARs) and retinoid X receptors (RXRs), each composed of a, p, and y subtypes. In addition, there is more than one isoform of each receptor subtype. RARy and RXRa are expressed predominantly in the skin. RARs can bind both all-trans-retinoic acid and 9-czs-retinoic acid, whereas RXRs interact with 9-czs-retinoic acid. In contrast, 13-cz's-retinoic acid shows low affinity for RARs. The nuclear receptors combine, with the attached retinoid molecules, to form homodimers (RAR/RAR, RXR/RXR) or heterodimers (RAR/RXR) and then subsequently bind to stretches of DNA known as response elements. As a result, gene transcription of the target gene is stimulated and the production of proteins, which may directly mediate the effects of the retinoid, is activated (Allen and Blox-ham 1989, Craven and Griffiths 1996, Orfanos et al. 1987,1997).

Hair Loss Prevention

Hair Loss Prevention

The best start to preventing hair loss is understanding the basics of hair what it is, how it grows, what system malfunctions can cause it to stop growing. And this ebook will cover the bases for you. Note that the contents here are not presented from a medical practitioner, and that any and all dietary and medical planning should be made under the guidance of your own medical and health practitioners. This content only presents overviews of hair loss prevention research for educational purposes and does not replace medical advice from a professional physician.

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