Age‐related changes in pro‐opiomelanocortin (POMC) and related receptors in human epidermis

Abstract

Much effort has been placed in cosmetic research for better understanding of the effects of ageing on skin's appearance, structure, mechanical properties and function. It is now of common knowledge that UV radiations induce pre-mature skin ageing notably in the epidermis where UV radiations induce keratinocyte differentiation. As UV radiations have also been shown to regulate the pro-opiomelanocortin (POMC) peptide family in the skin and because no study has been conducted so far to investigate the age-related changes in POMC and related receptors, we analysed POMC, MC-1R, MC-2R and MOR-1 at mRNA level and MC-1R, MC-2R and MOR-1 at protein level too in primary cultures of normal human keratinocytes obtained from female donors aged from 17 to 75 years old. Regarding the gene expressions, we observed that MC-1R, MC-2R and MOR-1 suffered a dramatic decrease after 50 years of age, whereas POMC increased five-fold. Western blot analysis confirmed these results except for MOR-1 whose expression appeared to decrease at older age, around 70 years old. Immunostainings specific to MC-1R, MC-2R and MOR-1 performed on full-thickness skin biopsies also revealed an intense staining in the basal and spinous layers of a 30-year-old donor, whereas no reactivity could be observed in a 60-year-old one. We conclude that POMC and POMC-related receptors suffer a dramatically disturbed balance with ageing and that this may be implicated in the general process of skin ageing.

Gene Expression Analysis of the Corticotrophin-releasing Hormone-proopiomelanocortin System in Psoriasis Skin Biopsies

“…Human MC 1R has the highest, and almost equal, affinity for a-MSH and ACTH, less affinity for ß-MSH, and least affinity for y-MSH (12). MC2R is tbe classical adrenocortical ACTH receptor (8) and its expression has been detected in keratinocytes (13) and adipocytes (14). MC3R expression in the skin has been shown in our previous studies, although its expression has not been localized to distinct cell types (15).…”

On the role of skin in the regulation of local and systemic steroidogenic activities

“…Even so, age-related changes affect morphological and functional properties of all endocrine glands; many are so intertwined that the reduced function in one gland adversely affects the others [21, 99, 232]. Aging also affects POMC and POMC-derived peptides, especially agonists for melanocortin receptor 1 (MC1R) and MC2R, which play key roles in skin biological systems [21, 233, 234]. Regulation of the cutaneous steroidogenic system is important for functions of the epidermis, as well as local immunity.…”

Facial skin-lightening benefits of the tetrapeptide Pro-Lys-Glu-Lys on subjects with skin types V-VI living in South Africa

“…We took a different approach and evaluate a peptide that had the potential to down‐regulate the expression of inflammatory cytokines as well as POMC 34 . POMC has been shown to undergo age‐related changes in primary keratinocyte cultures from human epidermis 45 . Thus, we are targeting the expression of genes involved in the melanogenic stimulus.…”