Supervisors: professor Sulev Kõks, PhD (TÜ füsioloogia instituut), professor Külli Kingo, PhD (TÜ nahahaiguste kliinik).
Opponent: dotsent Päivi Saavalainen, PhD (Helsingi Ülikool, Soome)
Vitiligo is an acquired disease, where melanocytes are destroyed and white patches appear on skin. The reasons are not jet fully understood. Patients are suffering from psychological stress and the risk for skin cancer increases. In vitiligo patients, the expression pattern has changed for genes that are involved in functioning of the hypothalamic-pituitary-adrenal axis (HPA axis) - the major pathway for stress response. Classically the HPA axis consists of CRH-POMC and glucocorticoid signaling pathways and is regulated by various cytokines and neurotransmitters. Our aim was to get more information about the nervous and immune system interactions in vitiligo patients. We measured mRNA and protein levels in skin and blood of vitiligo patients and healthy individuals; studied genes were associated to CRH-POMC-MCH system, melanogenesis regulating cytokines and dopamine pathway. In addition to our previous findings (decreased expression level of POMC system genes; essential activators of melanogenesis), we found that expression of endogenous opioid PNOC and its receptor has grown in lesional skin, also the MCH system (inhibits POMC system) expression has increased in patients. We showed changes in the expression pattern of interleukin-10 family cytokines and their receptors (regulating HPA axis) expression and other cytokines connected to melanogenesis and melanocyte growth and development. We provided supplemental confirmation that the neurotransmitter dopamine pathway may be involved in the pathogenesis of vitiligo - in addition to influencing the melanogenesis through the melanocortin pathway; dopamine may influence the skin homeostasis directly. In conclusion, in vitiligo patients, the functioning of cutaneous HPA axis has deviated from its normal state. The main inducer appears to be the changes in melanocortin system and the activating (cytokines) and inhibiting (dopamine) agents may attempt to restore the normal state of skin homeostasis.