• Objective:- The regulation of skin pigmentation

Birendra Kumar Singh

Schematic of human skin architecture from light- and darkpigmented skin types. From top to bottom: SC, stratum corneum; G, stratum granulosum; S, stratum spinosum; B, stratum basale; BM, basement membrane; D, dermis. Cell types: K, keratinocyte; M, melanocyte; F, fibroblast; shaded oval, melanin granule

BIOCHEMICAL CONSIDERATION (A chemist view of melanogenesis.Pathways for production of eumelanin and pheomelanin in melanocytes)

Regulation of constitutive skin pigmentation.Schematic of receptors, ligands, and other factors that

regulate pigmentation of human skin.

• Melanocyte density and differentiation is influenced by the environment including UV and factor secreted by neighboring keratinocyte.

• Constitutive skin pigmentation is determined by

1. The migration of melanoblast to that tissue during development

2. There survival and differentiation to melanocytes.

3. The expression/ function of enzymatic and structural constituents of melanosomes.

4. The synthesis of different type of melanin.

5. The transport of melanosomes to keratinocyte

6. And the distribution of melanin in suprabasal layer of skin.

Regulation of facultative skin pigmentation

The term coined for increased skin color due to some physiological factor.

Exposure to UV leads to increase the expression of MITF (the master transcriptional factor) and its downstream melanogenic protein like , Pmel17, MART-2,TYR, TRP1 and DCT.

Increased level of PAR2 in keratinocyte also result from exposure to UV, which increase uptake and distribution of melanosome to keratinocyte in the epidermis.

UV can also affect fibroblast in the dermis; growth factor secreted from those cells in response UV include HGF, bFGF and SCF all factors that stimulate pigmentation via there receptors on melanocytes.

The term coined for increased skin color due to some physiological factor.

Exposure to UV leads to increase the expression of MITF (the master transcriptional factor) and its downstream melanogenic protein like , Pmel17, MART-2,TYR, TRP1 and DCT.

Increased level of PAR2 in keratinocyte also result from exposure to UV, which increase uptake and distribution of melanosome to keratinocyte in the epidermis.

UV can also affect fibroblast in the dermis; growth factor secreted from those cells in response UV include HGF, bFGF and SCF all factors that stimulate pigmentation via there receptors on melanocytes.

Role of melanin in photoprotection of the skin

UV is harmful to human skin because of its production of various types of cellular damage, most notably oxidative damage and two major type of DNA damage; cyclobutane dimers and 6,4 –photoproducts

Protects from skin cancer

Lightly pigmented skin has high chance of melanomas than darker skin

UV induces significantly more apoptosis in dark skin than in fair skin , which suggest a more efficient removal of UV damaged cells.

UV is harmful to human skin because of its production of various types of cellular damage, most notably oxidative damage and two major type of DNA damage; cyclobutane dimers and 6,4 –photoproducts

Protects from skin cancer

Lightly pigmented skin has high chance of melanomas than darker skin

UV induces significantly more apoptosis in dark skin than in fair skin , which suggest a more efficient removal of UV damaged cells.

Disrupted regulation of skin pigmentation

The regulation of skin pigmentation sometimes goes awry leading to pigmentary disorders of many types.

Disruption in TYR

1. Hypopigmentation of skin ( Tyrp1 chaperone like protein)

Albinism

• OCA type 1 (TYR)

• OCA3 (TRYP1)

• OCA2(P)

• OCA4 (MATP)

• OA1 (due to impaired melanosome biogenesis)

Mutation in LRO function also affect pigmentation of melanocyte containing tissue and cause Hermansky Pudlak Syndrome

8 types in human 15 types in mice (related with protein trafficking)

The regulation of skin pigmentation sometimes goes awry leading to pigmentary disorders of many types.

Disruption in TYR

1. Hypopigmentation of skin ( Tyrp1 chaperone like protein)

Albinism

• OCA type 1 (TYR)

• OCA3 (TRYP1)

• OCA2(P)

• OCA4 (MATP)

• OA1 (due to impaired melanosome biogenesis)

Mutation in LRO function also affect pigmentation of melanocyte containing tissue and cause Hermansky Pudlak Syndrome

8 types in human 15 types in mice (related with protein trafficking)

Disrupted regulation of skin pigmentation

The acquired melanin pigmentary disorder can involve a lightening and darkening of the skin.

• E.g.. Leukoderma and Hypopigmentation

• Vitiligo (loss of melanocyte)

• Epidermal melanocytosis (increase no. of melanocyte that produce exceesive melanin)

• Epidermal melanosis (increased amout of melanin production by normal cell)

• Dermal melanosis (abnormal distribution of melanin)

The acquired melanin pigmentary disorder can involve a lightening and darkening of the skin.

• E.g.. Leukoderma and Hypopigmentation

• Vitiligo (loss of melanocyte)

• Epidermal melanocytosis (increase no. of melanocyte that produce exceesive melanin)

• Epidermal melanosis (increased amout of melanin production by normal cell)

• Dermal melanosis (abnormal distribution of melanin)

Approaches to regulate skin pigmentation

The regulation of human skin pigmentation has been long standing goal for cosmetics and pharmaceutical application.

A number of approaches has been tried to stimulate pigmentation but with little or no success because of the challenge in penetrating the skin barrier. i.e. stimulation of melanocyte function without affecting the other cell and vice versa.

Pigmentation of human skin has dramatic consequence at a variety of distinct level, such as social attraction and protection from the environment.

The skin is responsive to many factor that regulate its structure and appearance in an extremely complex manner.

The regulation of human skin pigmentation has been long standing goal for cosmetics and pharmaceutical application.

A number of approaches has been tried to stimulate pigmentation but with little or no success because of the challenge in penetrating the skin barrier. i.e. stimulation of melanocyte function without affecting the other cell and vice versa.

Pigmentation of human skin has dramatic consequence at a variety of distinct level, such as social attraction and protection from the environment.

The skin is responsive to many factor that regulate its structure and appearance in an extremely complex manner.