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MIM.176830 2p23.3

Thursday 23 February 2006

Corticotropin (ACTH), synthesized by the anterior pituitary gland, stimulates the adrenal cortex. Human ACTH has a molecular weight of 4,541 and contains 39 amino acids (Lee et al., 1961).

ACTH has structural similarities to melanotropin (melanocyte-stimulating hormone) (alpha-MSH). Human beta-melanotropin (beta-MSH) has 22 amino acid residues and a molecular weight of 2,661.

Work on the structure of the ACTH gene by restriction enzyme techniques showed that 6 hormones are derived from one gene: ACTH, lipotropin, alpha-MSH, beta-MSH, endorphin, and one other.

Thus, extensive amino acid differences between these hormones were not adequate evidence for their being distinct.

ACTH and beta-lipotropin (beta-LPH) are derived from a large precursor peptide. Each of these hormones is known to include smaller peptides having distinct biologic activities: alpha-melanotropin (alpha-MSH) and corticotropin-like intermediate lobe peptide (CLIP) are formed from ACTH; gamma-LPH and beta-endorphin are peptide components of beta-LPH. Beta-MSH is contained within gamma-LPH. The precursor peptide was called proopiomelanocortin (POMC) in 1979.

(POMC)-derived peptides in skin

The skin is a target organ and source for proopiomelanocortin (POMC)-derived peptides, such as alpha-melanocyte-stimulating hormone (alpha-MSH), which acts by binding to melanocortin receptors (MC-Rs).

Human dermal fibroblasts (HDFs) are a novel target for alpha-MSH. MC-1R is expressed by HDFs in vitro and in situ. MC-1R expression is also detectable in human connective tissue sheath fibroblasts (CTSFs) and in dermal papilla cells (DPCs) of the hair follicle, the latter concomitantly expressing MC-1R and MC-4R in vitro and in situ.

Both HDFs and DPCs are capable of generating POMC-derived peptides, although cell-specific differences exist in the expression of prohormone convertases and the amounts of POMC-derived peptides generated.

Functional studies have shown that alpha-MSH exerts anti-inflammatory actions in human fibroblastic skin cells by suppressing interleukin-1 (IL-1)-induced IL-8 production, activation of the transcription factor activator protein-1 (AP-1) and induction of intercellular adhesion molecule-1 by interferon-alpha.

In addition, alpha-MSH antagonizes the effect of transforming growth factor-beta1 (TGF-beta1) on collagen synthesis in HDFs in vitro and exerts antifibrogenic activity in a mouse model of cutaneous fibrosis.

Fibroblastic cells participate in the cutaneous POMC system in which alpha-MSH appears to act as a modulator of inflammatory and fibrogenic responses.

The biological activities of alpha-MSH in fibroblastic cells of the skin point towards novel clues in our understanding of the pathophysiology of fibrotic skin disorders and inflammatory diseases of the hair follicle and, finally, suggest innovative therapeutic options for the treatment of these conditions.

See also

- melanocortin receptors: MC1R, MC2R, MC3R, MC4R, MC5R


- Bohm M, Luger TA. Melanocortins in fibroblast biology—current update and future perspective for dermatology. Exp Dermatol. 2004;13 Suppl 4:16-21. PMID: 15507107