Proopiomelanocortin (POMC) and psychodermatology

Abstract

Psychodermatology is the crossover discipline between Dermatology and Clinical Psychology and/or Psychiatry. It encompasses both Psychiatric diseases that present with cutaneous manifestations (such as delusional infestation) or more commonly, the psychiatric or psychological problems associated with skin disease, such as depression associated with psoriasis. These problems may be the result either of imbalance in or be the consequence of alteration in the homoeostatic endocrine mechanisms found in the systemic hypothalamic-pituitary-adrenal axis or in the local cutaneous corticotrophin-releasing factor-proopiomelanocortin-corticosteroid axis. Alteration in either of these systems can lead to immune disruption and worsening of immune dermatoses and vice-versa. These include diseases such as psoriasis, atopic eczema, acne, alopecia areata, vitiligo and melasma, all of which are known to be linked to stress. Similarly, stress and illnesses such as depression are linked with many immunodermatoses and may reflect alterations in the body's central and peripheral neuroendocrine stress pathways. It is important to consider issues pertaining to skin of colour, particularly with pigmentary disorders.

FIGURE 1

Stylised hypothalamo‐pituitary‐adrenal (HPA) axis.

FIGURE 2

Gene structure and post‐translational processing of POMC. POMC in mammals consists of three exons, of which exons 2 and 3 are translated. PC1/2 break the parent POMC peptide into successively smaller peptides by cleavage at paired dibasic amino acid residues consisting lysine (K) and/or arginine (R). The final products are generated in a tissue specific manner, for example, α‐MSH and ACTH are not produced by the same cells in the pituitary. They also involve additional enzymatic post translational modifications, such as the acetylation of α‐MSH. The final products include the melanocortins (MSHs and ACTH), β‐end and CLIP. There are intermediate peptides whose biological function remains unclear, such as β‐LPH, γ‐LPH. CLIP, corticotrophin‐like intermediate peptide; PC1/2, prohormone convertases 1 and 2; POMC, proopiomelanocortin; α‐MSH, α‐melanocyte‐stimulating hormone; β‐end, β‐endorphin; β‐LPH, β lipotrophin; γ‐LPH, γ lipotrophin.

FIGURE 3

Natural melanocortins. These include the various MSH peptides and corticotrophin (ACTH). All share the common structure, His‐Phe‐Arg‐Trp (in bold) which facilitates binding to the MCR's. ACTH also contains the cleavage site, Lys‐Lys‐Arg‐Arg, which allows it to form α‐MSH and CLIP (see Figure 2). CLIP, corticotrophin‐like intermediate peptide; MCR's, melanocortin receptors; MSH, melanocyte‐stimulating hormone.

FIGURE 4

(a) Wild‐type mouse (+/+). (b) POMC homozygous mutant mice (−/−) become obese and develop a lighter hair colour on the ventral surface than sex and age matched wild‐type littermates (a). POMC, proopiomelanocortin.