A melanocortin receptor 1 and 5 antagonist inhibits sebaceous gland differentiation and the production of sebum-specific lipids.

Background: The melanocortin receptor-5 (MC5R) is present in human sebaceous glands, where it is expressed in differentiated sebocytes only. The targeted disruption of MC5R in mice resulted in reduced sebaceous lipid production and a severe defect in water repulsion.

Objective: To investigate the physiological function of MC5R in human sebaceous glands.

Melanocortin-5 receptor and sebogenesis.

The melanocortins (α-MSH, β-MSH, γ-MSH, and ACTH) bind to the melanocortin receptors and signal through increases in cyclic adenosine monophosphate to induce biological effects. The melanocortin MC(5) and MC(1) receptors are expressed in human sebaceous glands, which produce sebum, a lipid mixture of squalene, wax esters, triglycerides, cholesterol esters, and free fatty acids that is secreted onto the skin. Excessive sebum production is one of the major factors in the pathogenesis of acne.

Sebum analysis of individuals with and without acne.

A pilot study was conducted to compare lipid components of sebum from unaffected and acne-affected individuals. Nine males, 15-20 years old, with no acne, or with moderate to severe acne, were recruited. Facial images were taken with regular, polarized and fluorescent lights for each subject.

The role of keratinocyte growth factor in melanogenesis: a possible mechanism for the initiation of solar lentigines.

Solar lentigines (SLs) are hyperpigmentary lesions presented on sun-exposed areas of the skin and associated with ageing. The molecular mechanism of SL initiation is not completely understood. Ultraviolet B (UVB) stimulates keratinocytes to produce interlukin-1 alpha (IL-1α), which then induces keratinocyte growth factor (KGF) secretion; therefore, we examined their possible roles in the induction of SLs.

Melanocortin-5 receptor: a marker of human sebocyte differentiation.

Melanocortin receptors (MC1R-MC5R) and their ligands (melanocyte-stimulating hormone (MSH) and adrenocorticotrophin hormone (ACTH)) have been shown to influence physiological functions of cells and organs, including exocrine glands. Since relatively little is known about MC5R expression and function in the human sebaceous gland, we examined expression of MC5R by immunohistochemistry and RT-PCR in human sebaceous cells in vivo and in vitro. In human skin, MC5R was detected only in differentiating, lipid-laden sebaceous cells but not in basal, undifferentiated sebaceous cells.