pigmentation

pigmentation in the body is due to different forms of melanin, the name for a group of closely related substances, of different shades of black and brown, that are synthesized in body cells (melanocytes), mostly from the amino acid tyrosine. The most widespread type of melanin is responsible for skin colour; the melanocytes, deep in the epidermis, make it, and transfer it into the keratin cell layer of the skin. In ‘white’ skin, freckles and moles are areas of concentrated pigmentation; exposure to sunlight results in stimulation of the melanocytes and hence to a ‘tan’. Excessive stimulation can sometimes produce a melanoma, which can have serious consequences if not recognized and treated at an early stage.

Variations in eye and hair colour are due to different types of melanin. As well as the visible sites, there is also melanin pigmentation in the choroid coat of the eye, the vascular layer that invests all but the front part of the eyeball, behind and around the retina; also in the cochlea and vestibule of the inner ear, variably in the adrenal glands, and in the substantia nigra of the brain. It is normal for pigmentation to increase during pregnancy, particularly in the areola of the nipples, and in the ‘stretch marks’ on the abdomen.

Abnormalities of pigmentation are of interest in understanding its normal significance. Vitiligo is a relatively common autoimmune condition, in which melanocytes are patchily destroyed, causing totally white areas in the skin. Provided that sun creams can be used for protection, the problem is only — though disturbingly — a cosmetic one, seriously so for dark-skinned people; small patches of depigmentation can also occur in the iris. In albinos, pigmentation is defective everywhere: not only in the skin, hair, and iris but also behind the retina, with associated visual problems; melanocytes are present, but melanin synthesis is impossible due to congenital lack of the enzyme tyrosinase.

Excessive pigmentation can be caused by oversecretion of adrenocorticotrophic hormones (ACTH) and an associated melanocyte-stimulating hormone (MSH) from the pituitary gland.

In 1855 Thomas Addison, physician at Guy's Hospital, London, reported ‘… a peculiar change of colour in the skin, occurring in connection with a diseased condition of the “supra-renal capsules”.’ It was some considerable time before this link between pigmentation and disease of the adrenal glands was to be explained. We now know that if the adrenal cortex fails to maintain its normal output of hormones (notably cortisol), the low levels in the blood are detected in the hypothalamus, through the normal feedback mechanism, and ‘interpreted’ as requiring a stimulus to action; thus the anterior pituitary is signalled to release more ACTH, which vainly flogs the dying horse. Whenever ACTH synthesis and secretion are increased, there is linked release of the closely associated MSH, and hence an increase in melanin production in the skin. This explanation is confirmed by observation of excessive pigmentation in other conditions in which ACTH secretion is excessive, and absence of such pigmentation when failure of the adrenal cortex is secondary to a failure of ACTH secretion itself. Primary disorder of the adrenal cortex — hypoadrenalism or ‘Addison's disease’ — was formerly most often due to tuberculosis; it is now rare, and usually the result of autoimmune destruction of the hormone-producing cells.

The link between these abnormal situations and the physiological significance of melanin secretion seems at first sight obscure. Whereas ACTH, and the adrenal secretions that it promotes, have now for long been recognized as counteracting the consequences to the body of actual or potential damage or stress, more recently it has been shown that there is a range of associated substances released from the pituitary gland along with ACTH, which may all contribute, one way and another, to protective responses. Melanin in the skin is best known for its protection against UV light; it does this by taking up ‘free radicals’. Since these are released in a variety of other potentially harmful situations, not just in exposure to sunlight, melanin may have additional protective functions.

Sheila Jennett

See also adrenal gland; albinos; eyes; freckles; hair; pituitary gland; skin; skin colour; sun and the body.