How hormones may modulate human skin pigmentation in melasma: An in vitro perspective

Abstract

Melasma is a common acquired hyperpigmentary disorder occurring primarily in photo‐exposed areas and mainly affecting women of childbearing age. To decipher the role of sex hormones in melasma, this viewpoint reviews the effects of sex hormones on cutaneous cells cultured in monolayers, in coculture, in 3D models and explants in the presence or the absence of UV. The data show that sex steroid hormones, especially oestrogen, can modulate in vitro pigmentation by stimulating melanocytes and keratinocyte pro‐pigmentary factors, but not via fibroblast or mast cell activation. In vitro data suggest that oestrogen acts on endothelial cell count, which may in turn increase endothelin‐1 concentrations. However, data on explants revealed that sex steroid even at doses observed during pregnancy cannot induce melanogenesis alone nor melanosome transfer but that it acts in synergy with UVB. In conclusion, we hypothesize that in predisposed persons, sex steroid hormones initiate hyperpigmentation in melasma by amplifying the effects of UV on melanogenesis via direct effects on melanocytes or indirect effects via keratinocytes and on the transfer of melanosomes. They also help to sustain hyperpigmentation by increasing the number of blood vessels and, in turn, the level of endothelin‐1.

Melasma Show Up in Contraceptive Pills Acceptors

“…9 This result accordance with the theoretical basis, that longer use of contraceptive pills will increase the incidence of melasma through several mechanism, such as estradiol that play a role on increace the MCR 1 (melanocortin receptor-1) on melanocytes, tyronase level, and mRNA level. 10,11 Tyronase enzyme play a role in the catalytic reaction, change the tyrosine become L3,4 DOPA (dihydroxyphenilalanine), the increase of tyronase will affect the melanin formation to become more and more. Melanogenesis start with oxidation of aminotyrosine acid become Ldihidroksifenilalanin (L-DOPA) and then become dopaquinone.…”

Asoprisnil, a Selective Progesterone Receptor Modulator (SPRM), Inhibits Melanosome Export in B16F10 Cells and HEMn-DP Melanocytes

“…Furthermore, our results also demonstrate that AP is nontoxic to keratinocytes at the low micromolar doses at which it inhibited melanogenesis. Several earlier reports evidence the role of hormones in affecting skin pigmentation [ 11 , 12 , 28 ], and it has been documented that progesterone might be useful in inclusion in oral contraceptives to counteract the development of melasma that is often attributable to estrogens [ 29 ]. A higher expression of progesterone receptor (PR) has been documented in epidermal skin lesions in contrast to healthy skin [ 30 ].…”

Targeting steroid receptor RNA activator (SRA), a long non-coding RNA, enhances melanogenesis through activation of TRP1 and inhibition of p38 phosphorylation

“…Melasma, a facial skin disease with abnormally enhanced melanin synthesis, is not uncommon in middle-aged women. It has been hypothesized that in predisposed persons, sex steroid hormones may initiate hyperpigmentation in melasma by amplifying the effects of UV on melanogenesis [32]. In fact, it has been found that estradiol [33] and diethylstilbestrol (DES) [34] upregulate tyrosinase and enhance melanin synthesis in B16 cells.…”