Vitamin A and D as hormones

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Horm Metab Res. 2007 Feb;39(2):71-84.

Vitamins as hormones.

Reichrath J, Lehmann B, Carlberg C, Varani J, Zouboulis CC.

1Department of Dermatology, The Saarland University Hospital,

Homburg, Germany.

Vitamins A and D are the first group of substances that have been

reported to exhibit properties of skin hormones, such as organized

metabolism, activation, inactivation, and elimination in specialized

cells of the tissue, exertion of biological activity, and release in

the circulation. Vitamin A and its two important metabolites,

retinaldehyde and retinoic acids, are fat-soluble unsaturated

isoprenoids necessary for growth, differentiation and maintenance of

epithelial tissues, and also for reproduction. In a reversible

process, vitamin A is oxidized IN VIVO to give retinaldehyde, which

is important for vision. The dramatic effects of vitamin A analogues

on embryogenesis have been studied by animal experiments; the

clinical malformation pattern in humans is known. Retinoic acids are

major oxidative metabolites of vitamin A and can substitute for it in

vitamin A-deficient animals in growth promotion and epithelial

differentiation. Natural vitamin A metabolites are vitamins, because

vitamin A is not synthesized in the body and must be derived from

carotenoids in the diet. On the other hand, retinoids are also

hormones - with intracrine activity - because retinol is transformed

in the cells into molecules that bind to and activate specific

nuclear receptors, exhibit their function, and are subsequently

inactivated.

The mechanisms of action of natural vitamin A metabolites on human

skin are based on the time- and dose-dependent influence of

morphogenesis, epithelial cell proliferation and differentiation,

epithelial and mesenchymal synthetic performance, immune modulation,

stimulation of angiogenesis and inhibition of carcinogenesis. As

drugs, vitamin A and its natural metabolites have been approved for

the topical and systemic treatment of mild to moderate and severe,

recalcitrant acne, photoaging and biologic skin aging, acute

promyelocytic leukaemia and Kaposi's sarcoma.

On the other hand, the critical importance of the skin for the human

body's vitamin D endocrine system is documented by the fact that the

skin is both the site of vitamin D (3)- and 1,25-dihydroxyvitamin D

(3) [1, 25(OH) (2)D (3)]-synthesis and a target organ for 1,25(OH) (2)

D (3). 1,25(OH) (2)D (3) is not only essential for mineral

homeostasis and bone integrity, but also for numerous further

physiologic functions including regulation of growth and

differentiation in a broad variety of normal and malignant tissues,

including cells derived from prostate, breast and bone. In

keratinocytes and other cell types, 1,25(OH) (2)D (3) regulates

growth and differentiation.

Consequently, vitamin D analogues have been introduced for the

treatment of the hyperproliferative skin disease psoriasis. Other

newly detected functions of vitamin D analogues include profound

effects on the immune system as well as protection against cancer and

other diseases, including autoimmune and infectious diseases, in

various tissues.

Current investigation of the biological effects of vitamin D

analogues are likely to lead to new therapeutic applications that,

besides cancer prevention, may include the prevention and treatment

of infectious as well as of inflammatory skin diseases. This review

summarizes existing knowledge on vitamins A and D, the major vitamin-

hormones of the skin.

PMID: 17326003 [PubMed - in process]