Vitamin A (including the active form — retinoic acid, RA) plays a particular role in the life of melanocytes. Recall that melanocyte arise during embryogenesis from neural crest cells, i.e., these cells are direct "relatives" of epithelial and nerve cells. In the skin, two groups of melanocytes are distinguished. Interfollicular melanocytes on the basal membrane are highly differentiated cells that produce melanin to protect the skin from ultraviolet light. Melanocytes of the second group are responsible for hair color and are localized in the exact locations as the hair follicle stem cells, particularly in the bulb area. Among the melanocytes of the hair follicle, there are also less mature ones.

The effect of retinoids on melanocytes has been studied in many experiments, but the results are contradictory. For example, in cultures of melanocytes isolated from hair follicles, trans-RA increased, decreased, or had no effect on melanin production.

Physiologic doses of RA administered at the beginning of melanocyte differentiation or throughout the process promoted cell maturation. However, if RA was administered at later stages, it inhibited the maturation process. Moreover, while physiologic levels of all-trans RA increased the expression of melanocyte-inducible transcription factor (MITF) and tyrosinase-related protein 1 (TRP-1) in immature melanocytes, they decreased the expression of these genes in mature cells (see Figure).

Treatment of cultured mature human melanocytes with all-trans RA caused morphological changes in the cells: they became darker and flatter. However, after RA removal, melanocytes returned to their original state.

It was found that trans-PA at pharmaceutical doses stopped UV-stimulated melanin synthesis and reduced the expression and activity of tyrosinase, an enzyme involved in melanin production. In contrast, another retinoid, 9-cis-RA, increased the expression of MITF and tyrosinase in cultured melanocytes.

Melanocytes, like other cells, can synthesize RA themselves from endogenous precursors, such as retinol, retinal, and retinol esters, depending on their needs. However, treating mature melanocytes with exogenous trans-RA introduces an imbalance in this process.

These and many other facts suggest that the use of retinoids to influence skin pigmentation through suppression of melanogenesis remains under great question.

As for some brightening and skin tone equalization on the background of retinol cosmetics, these effects are indeed observed. However, they are associated not with active suppression of melanin synthesis but with the renewal of keratinocytes and stratum corneum in the epidermis. But this is a different story.

Reference

VanBuren C.A., Everts H.B. Vitamin A in Skin and Hair: An Update. Nutrients. 2022; 14(14): 2952.