Biochemistry and morphological picture
Pigment synthesis is a biochemical cascade based on the oxidation of the amino acid tyrosine. Under the action of the specific enzyme tyrosinase, tyrosine is converted into dihydroxyphenylalanine (DOPA), from which melanin is subsequently formed.
Two pools of cells participate in tissue metabolism:
- Melanocytes are cells that directly synthesize the pigment.
- Melanophages are cells that phagocytose (engulf) preformed melanin.
For histological verification of melanin in the laboratory, the argentaffin reaction is used. Its principle is based on the ability of the pigment to reduce an ammoniacal silver nitrate solution. As a result, metallic silver precipitates, which allows clear visualization of melanin accumulations under a microscope.
Regulation of melanogenesis
The process of melanin formation is under the strict control of the endocrine and nervous systems, and also depends on physical environmental factors.
Activators of synthesis (stimulators):
- Pituitary hormones: $\beta$-lipotropin, melanocyte-stimulating hormone (MSH), and adrenocorticotropic hormone (ACTH).
- Thyroid hormones.
- Sex hormones.
- Mediators of the sympathetic nervous system.
- Physical factors: ultraviolet (UV) rays.
Inhibitors of synthesis (suppress the process): Inhibition of pigment production is provided by melatonin and mediators of the parasympathetic nervous system.
End products of pigment metabolism are eliminated from the body via two pathways: through the kidneys and through the intestines.
Classification of metabolic disorders
Melanin metabolic pathologies are systematized according to two main criteria:
- By origin: congenital and acquired.
- By prevalence in the body: local and generalized.
Conditions in which enhanced melanogenesis occurs are called hyperpigmentations or melanoses. A striking example of congenital generalized melanosis is xeroderma pigmentosum. Among acquired generalized forms, the classic variant is Addison's disease.
Pathogenesis of Addison's (bronze) disease
Addison's disease is an acquired generalized melanosis. The basis of the disease is bilateral adrenal lesion. The etiology of the process is diverse: autoimmune destruction, tuberculosis infection, amyloidosis, as well as primary tumors or metastases.
The mechanism of hyperpigmentation development is as follows:
- Due to the destruction of adrenal tissue, the blood level of cortisol sharply decreases.
- By a feedback mechanism, the pituitary gland begins to intensely synthesize ACTH.
- Excess ACTH has a pronounced melanin-stimulating effect.
- Activation of the tyrosinase enzyme occurs.
- Massive synthesis of melanin is triggered, which is deposited in the skin and mucous membranes.
Microscopic examination of skin biopsies (standard hematoxylin and eosin staining) clearly reveals excessive pigment deposition, confirming hyperpigmentation.
Briefly: answers to topical questions
Which pathologies belong to local acquired melanoses?
Local (focal) acquired melanoses include various types of hyperpigmentation of restricted tissue areas.
This group includes the following pathologies:
- Freckles — local skin hyperpigmentation.
- Melasma — a focal form of melanosis.
- Lentigo — local hyperpigmentation.
- Nvocellular nevus — a mole.
- Melanosis coli — focal acquired hypermelanosis in patients with chronic constipation.
In addition, focal hyperpigmentations occur as comorbid conditions in pituitary adenomas, hyperthyroidism, and diabetes mellitus.
What pathologies are examples of congenital and acquired hypomelanosis?
Hypopigmentations include albinism and vitiligo.
| Characteristic | Albinism | Vitiligo |
|---|---|---|
| Prevalence | Generalized disorder | Local manifestation of hypopigmentation |
| Inheritance and etiology | Autosomal recessive inheritance pattern | Familial nature, trauma, endocrine and autoimmune diseases, outcome of inflammatory and necrotic processes |
| Mechanism | Absence or decrease in tyrosinase activity; melanocytes are present | Absence of melanocytes in the lesions |
Albinism is accompanied by a decrease or absence of pigmentation of the skin, hair, iris, and retina. Vitiligo is characterized by clearly demarcated, often symmetrical depigmented skin areas.
How to memorize melanin synthesis stimulators? Think of a summer vacation: UV rays (sun), sympathetic nervous system (activity), sex hormones (romance), and the thyroid gland (energy). And the process is inhibited by melatonin (sleep) and the parasympathetic system (rest in the shade).
Class and exam questions
How to prove histologically that we are dealing specifically with melanin?
For this, the argentaffin reaction is used. Melanin has the ability to reduce an ammoniacal silver nitrate solution to metallic silver, which is clearly visible on the slide.
What is the difference between melanocytes and melanophages?
Melanocytes are cells that directly synthesize pigment from tyrosine. Melanophages do not produce pigment themselves; they merely phagocytose (engulf) preformed melanin.
Why does the skin darken in adrenal insufficiency?
The feedback-loop decrease in cortisol levels stimulates ACTH production by the pituitary gland. ACTH activates tyrosinase and triggers excessive synthesis of melanin in the skin and mucous membranes.
What else to study on this topic
- Xeroderma pigmentosa: features of congenital widespread melanosis.
- Adrenochrome and the pigment of enterochromaffin cell granules as representatives of the tyrosinogenic group.
- Etiological factors of adrenal damage (tuberculosis, amyloidosis, tumors).
- Mechanisms of excretion of melanin metabolic products through the kidneys and intestines.
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