β-Endorphin as a Regulator of Human Hair Follicle Melanocyte Biology

Abstract

The pro-opiomelanocortin (POMC)-derived peptides, alpha-melanocyte-stimulating hormone, and adrenocorticotropic hormone, are important mediators of human skin pigmentation via action at the melanocortin-1 receptor. Recent data suggests that such a regulatory role also exists for the endogenous opiate, beta-endorphin (beta-END). A role for this beta-END in the regulation of follicular pigmentation, however, has not been determined. This study was designed to examine the involvement of the beta-END/mu-opiate receptor system in human follicular melanocyte biology. We employed RT-PCR, and immunohisto/cytochemistry and immunoelectron microscopy using beta-END and mu-opiate receptor specific antibodies and a functional role for beta-END was assessed by direct stimulation with the peptide. This study has demonstrated that human hair follicle melanocytes (HFM) express mRNA for the mu-opiate receptor and POMC. Furthermore, beta-END and its high affinity mu-opiate receptor are expressed at the protein level in glycoprotein100-positive follicular melanocytes and as a function of their anatomic location and differentiation status during the hair growth cycle. Functional studies revealed that beta-END is a modifier of HFM phenotype via its ability to upregulate melanogenesis, dendricity, and proliferation. These findings suggest a new regulatory role for beta-END in human HFM biology, providing a new research direction into the fundamental regulation of human hair pigmentation.

Corticotropin releasing hormone and the skin

“…The POMC system is fully expressed in the human scalp hair follicle pigmentary unit and the behavior of follicular melanocytes in vitro is modulated via action at the MC1-R (by alpha-MSH and ACTH) and the mi-opiate receptor (by beta-endorphin) pathways (90,91). Under our own cell culture conditions, beta-endorphin was as potent as the traditional melanocortins ACTH and alpha-MSH at inducing melanogenesis and dendricity in follicular melanocytes (90,91).…”

“…(6,7,20,24,51,70,(72)(73)(74)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95). These studies indicate that human hair follicles are also peripheral endocrine mini-organs that are both a source (including a metabolizing source) and a target of multiple neuro-steroido-hormones (4,74,91,(95)(96)(97)(98).…”

“…Under our own cell culture conditions, beta-endorphin was as potent as the traditional melanocortins ACTH and alpha-MSH at inducing melanogenesis and dendricity in follicular melanocytes (90,91). Because the supply of POMC may be regulated locally via CRH, we assessed the role of CRH, urocortin and receptor-selective CRH-related peptides in the human hair follicle and its pigmentary unit (91,102).…”

Proopiomelanocortin (POMC), the ACTH/ melanocortin precursor, is secreted by human epidermal keratinocytes and melanocytes and stimulates melanogenesis

“…Cells were incubated at 37°C in a 5% CO 2 atmosphere and medium was replenished every third day. Hair follicle melanocytes were established from normal human haired scalp tissue (3 females 1 male; 55-66 years, mean 59 years) as described previously (20,35,36) and grown as for epidermal melanocytes above.…”

Prostaglandin-E(2) is produced by adult human epidermal melanocytes in response to UVB in a melanogenesis-independent manner.

“…of keratinocytes and after removal of contaminating fibroblasts with 150 lg ⁄ ml geneticin sulphate (G418) in 48 h cycles at the p0 to p1 stage of primary culture (Halaban and Alfano, 1984)] in a mixture of keratinocyte-serum free medium (PromoCell, Heidelberg, Germany) supplemented with bovine pituitary extract (BPE) (4 lg ⁄ ml), epidermal growth factor (EGF) (0.125 ng ⁄ ml), insulin (5 lg ⁄ ml), hydrocortisone (0.33 lg ⁄ ml), epinephrine (0.39 lg ⁄ ml), transferrin (10 lg ⁄ ml), penicillin (100 U ⁄ ml) ⁄ streptomycin (100 lg ⁄ ml) and L-Gln (2 mM) and Eagle's minimal essential medium supplemented with FBS (2%), 1x concentrated non-essential amino acid mixture, penicillin (100 U ⁄ ml) ⁄ streptomycin (100 lg ⁄ ml), L-Gln (2 mM), bFGF (5 ng ⁄ ml) and ET-1 (5 ng ⁄ ml) as previously described (Kauser et al, 2004). Melanocyte identity was confirmed by gp-100 immunostaining of cell monolayers at passage 1.…”