Biochemistry and Morphological Features
Pigment synthesis is a biochemical cascade centered 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 cell pools participate in tissue metabolism:
- Melanocytes — cells that directly synthesize the pigment.
- Melanophages — cells that phagocytose (ingest) preformed melanin.
For histological verification of melanin in the laboratory, the argentaffin reaction is used. Its principle is based on the pigment's ability to reduce an ammoniacal silver nitrate solution. As a result, metallic silver precipitates, allowing clear visualization of melanin aggregates under a microscope.
Regulation of Melanogenesis
Melanin production is under 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.
- Sympathetic nervous system neurotransmitters.
- Physical factors: ultraviolet (UV) rays.
Inhibitors of Synthesis (Suppressors): Inhibition of pigment production is provided by melatonin and parasympathetic nervous system neurotransmitters.
Utilized products of pigment metabolism are excreted from the body via two main routes: the kidneys and the gastrointestinal tract.
Classification of Metabolic Disorders
Pathologies of melanin metabolism are classified according to two main criteria:
- By origin: congenital and acquired.
- By bodily distribution: local and generalized.
Conditions involving enhanced melanogenesis are termed hyperpigmentations or melanosis. A classic example of congenital generalized melanosis is xeroderma pigmentosum. Among acquired generalized forms, a classic variant is Addison's disease.
Pathogenesis of Addison's (Bronze) Disease
Addison's disease is an acquired generalized melanosis. The underlying cause is bilateral destruction of the adrenal glands. The etiology is diverse: autoimmune destruction, tuberculosis, amyloidosis, as well as primary tumors or metastases.
The mechanism of hyperpigmentation development is as follows:
- Destruction of adrenal tissue leads to a sharp drop in blood cortisol levels.
- Via negative feedback, the pituitary gland increases ACTH synthesis.
- Excess ACTH exhibits marked melanin-stimulating activity.
- The enzyme tyrosinase is activated.
- Massive melanin synthesis is triggered and deposited in the skin and mucous membranes.
Microscopic examination of skin biopsies (standard hematoxylin and eosin staining) clearly reveals excessive pigment deposition, confirming hyperpigmentation.