• Institute of Biology and Immunology of Reproduction
      "Acad. Kiril Bratanov"

      • Scientific achievements

        Most relevant scientific achievements

        • Studies on the pineal hormone melatonin and its relevance as a circadian regulator of physiological functions have revealed role in neuroendocrine-immune homeostasis through control on glucocorticoid secretion in supreme brain centers and through direct inhibitory action on lymphocyte proliferation. The direct action of melatonin in primary and secondary immune tissue has been confirmed by several methods including radioligand-receptor analysis, autoradiography, Western and immune blot analysis, ICH and ISHH. The established biochemical characteristics correspond to those found for the trans-membrane G-protein coupled receptor (Mel 1А) in neural tissue. Distinct diurnal variations in the binding capacity of the receptors in rat spleen and thymus have been found which most probably reflect the chronomodulating action of the hormone on the functions of immunocompetent T-lymphocytes. Increased endogenous levels of glucocorticoids due to immobilization stress participated in modulation of the receptor characteristics for melatonin in secondary immune tissue, sensitized with T-dependent antigen.
        • In longitudinal studies of patients with disbalanced glucocorticosteroid and hypophysiotropic secretion (Cushing’s syndrome), recruited at the Center of Endocrinology, MU, Sofia, several endocrine and immune parameters have been correlated to circadian melatonin pattern in peripheral blood and saliva. Except for the disturbances in the gonadotropin secretion (luteinizing, follicle-stimulating hormones and prolactin), we found significant differences of clinical relevance concerning chronobiological parameters of the endogenous rhythm of melatonin and cortisol (acrophase, amplitude, % rhythm) associated to different etiology of the disease. We were able to show that the abnormal encreased activity and the absence of regular circadian rhythm of the glucocorticoid axis are accompanied by disturbances in the rhythm of melatonin secretion and the presence of altered pro-inflammatory immune response.
        • In collaboration with the Laboratory of Endocrinology and Metabolism, Albert Einstein College, New York, the modulation role of thiazolidininedions (insulin-sensitizing pharmaceutical agents, agonists of PPAR-gamma) on the signal pathways of insulin and expression of StAR protein in mixed ovarian cultures has been investigated. A model for interaction with potential significance in the physiological and the pathological response to insulin has been proposed. The action of insulin and TZDs mediated by their receptors results in stimulation of the StAR protein in ovary tissue and activate IRS-1 – a key component of the insulin signal pathway. These results contribute to the clarification of the therapeutic role of insulin-sensitizing agents in relation to reproductive problems with metabolic component in women.
        • The role of chronobiological controlled factors of antioxidant protection against highly reactive oxidation radicals, especially in male reproductive system, and their importance in the etiology of idiopatic male infertility has been studied. Obtained pilot results indicate that melatonin has relevance to the fertilization capacity of human spermatozoa, most probably through modulation of the balance of growth factors /EGF, testosterone, esradiol/ and enzymes /aromatase, NOS-synthase/ in semen plasma.
        • The Radioisotope laboratory for hormonal diagnostics at the Department of Immunoneuroendocrinology is performing complex radioimmunological and radioligand-receptor analyses of peptide and non-peptide hormones and biologically active compounds. By using high sensitive direct RIA methods, in-vitro models for examination of cultivated tissues and cells from female and male reproductive tissue have been established and validated, which allow investigation of reproductive characteristics at cellular level. Pilot studies on the cryopreservation of human ovary tissue based on the use of these models have been awarded in 2003 with Signum Laudis pro Sciencae Merriti of Medical University of Sofia for contribution to the clinical medical science.
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