Melanin

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MELANOCYTES

Definition of Melanocyte:
•Dendritic cells.

•Epidermis → Stratum basalis.

•Synthesize melanosomes.
EMBRYOLOGY OF MELANOCYTE
 Neural crest-derived (ectoderm).

 Migrate into:

1-Epidermis & hair follicle.

2-Uveal tract(eye).

3-Leptomeninges
(arachnoid & pia maters).

4-Cochlea(inner ear).
Genetic disorders of hypopigmentation
 Albinism
→Visual abnormalities

 Waardenburg syndrome
→Congenital deafness, auditory symptoms,
heterochromia iridis & aseptic meningitis.

Due to absence of melanin


EMBRYOLOGY OF MELANOCYTE
 Embryo melanocytes in the dermis.

 At the end of gestation migrate to epidermis.

Mongolian spot
Failure of migration of melanocytes from the
dermis in to the epidermis.
HISTOLOGY
Shape
• Dendritic cell.

• Dendritic processes
→transfer melanin to keratinocytes.

• Store melanin in cytosolic organelles


”melanosomes” → keratinocytes.
HISTOLOGY
Site
Between basal keratinocytes:

• 1melanocyte / 5-10 basal keratinocytes.


• 1melanocyte / 36 keratinocytes.
HISTOLOGY
Special stain
1- Silver stain → black.

2-Dopa reaction → dark brown - black.


HISTOLOGY
Immunohistochemical
1- Melan-A (the most specific).

2-HMB-45 (specific).

3-S-100 protein (non specific).


HISTOLOGY
STAGES OF MELANOSOMES
HISTOLOGY
STAGES OF MELANOSOMES
Physiology
of pigmentation
NORMAL SKIN COLOUR DEPENDS ON:

1-Melanin →brown-black.

2- Haemoglobin
(oxygenated →red , reduced → blue).

3-Carotenoids (yellow-orange).

Thickness of the horny layer

Normal skin pigmentation


FUNCTIONS OF MELANIN
1) Protection against UV-induced
DNA damage .

2) Gives the skin, eyes & hair their


color.

3) Neutralizer of toxins & free


radical.
TYPES OF
MELANOCYTES
1- SECRETORY :

•Transfer melanosomes to
surrounding keratinocytes .

2- NON-SECRETORY :

•Not transfer melanosome.


•Redistribute them into dendrites .
TYPES OF MELANIN PIGMENTATION
•Constitutive:
Genetically.

•Facultative (inducible):
Sun exposure.
TYROSINASE
• The key enzyme for melanin synthesis.
• In melanosomes.
• Binds two copper atoms
“important for tyrosinase activity”.

Rare cases of copper deficiency

Diffuse cutaneous hypopigmentation


MITF
(MICROPHTHALMIA-ASSOCIATED TRANSCRIPTION FACTOR)

• MITF gene is the master gene for melanocyte


survival.
• It is the key factor regulating the transcription of
the major melanogenic proteins .

Mutations in MITF :
Waardenburg syndrome type 2
Tietz syndrome
MC1-R (MELANOCORTIN 1 RECEPTOR)
• ACTH & MSH activate MC1-R.
• MC1-R →↑melanogenesis.

Addison’s disease
Generalized hyperpigmentation
SYNTHESIS OF MELANIN
1) Transcription of proteins(required for melanin synthesis).

2) Sorting of proteins into


melanosomes.

3)Melanin synthesis within


the melanosome

4)Transport of the
mature melanosomes to the
tips of melanocyte dendrites.

5)Transfer of melanosomes to keratinocytes.


SYNTHESIS OF MELANIN

Tyrosinase

L-tyrosine L-dopa L-dopa-quinone


TYPES OF MELANIN
1-Eumelanin 2-Pheomelanin

Colour Brown, black Red-yellow

Solubility Insoluble Alkali soluble


Sex Equal Females

Site Any site •Lips, nipples.


•Glans of the penis.
•Vagina.
Carcinogenic Less 
TRANSFER OF MELANOSOME TO
KERATINOCYTE
• Melanosomal membrane fuse with melanocyte plasma
membrane
Exocytosis: •→ intercellular space
•→ phagocytosis by surrounding keratinocytes.

•Projection of dendrites into keratinocyte


Cyto-phagocytosis: •→ keratinocytes phagocytose melanocyte dendritic tip.

•Melanocyte & keratinocyte plasma membrane.


Fusion •→Space through which melanosomes are transferred .

•Melanosome-filled vesicles.
Shedding •→ phagocytosis of the vesicles by keratinocytes.
Factors
affect↑melanogenesis
FACTORS AFFECT
MELANOGENESIS
• Melanocyte density/square mm ranges from 550-1500.
• The highest concentration within face & genitalia.

Melanocyte density
→ constant in different ethnic groups.

Pigmentation
NOT depend on melanocyte number
FACTORS
AFFECT↑MELANOGENESIS
ETHNIC DIFFERENCES
IN SKIN COLOUR

Capacity of
melanocytes
to synthesis melanin
FACTORS
AFFECT↑MELANOGENESIS
1) UV irradiation (direct effect).

2) keratinocyte-activate-melanocyte pathway
(indirect effect).

3)Hormones:
1- MSH 2- ACTH 3- Estrogens
Keratinocyte → ↑ melanocytes

UV Irradiation or any injury to Keratinocyte


↑ plasmin
1-↑Leukotrienes.
2- ↑Fibroblast growth factor (FGF).

↑Melanogenesis
FACTORS
AFFECT↑MELANOGENESIS
SKIN TYPE
SkinTan
colour
(Genetic)
(Sun)
FACTORS
AFFECT↑MELANOGENESIS
MELANOSOMES
MELANOSOMES

Lightly pigmented skin Dark pigmented skin


Melanosomes Basal cell layer. •Basal cell layer.
tranfer •Whole epidermis.
HISTOLOGY
STAGES OF MELANOSOMES
EFFECT OF SUN ON SKIN
PIGMENTATION
THANK YOU

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