NEW APPROACHES TO ATTACK THYROID GLAND DISFUNCTION

L. Bondarenko, E. Somova, I. Komarova, V. Scherbakova, and E. Rom-Bugoslavskaya
Laboratory of Endocrine Diseases Biochemistry
Ukrainian Research Institute of Endocrine Diseases Pharmacotherapy
10, Artema Str., Kharkov 61002, Ukraine

E-mail: fez@email.itl.net.ua , fax: 38572475121

Thyroid hormones are well-known to have wide-ranging biological actions in the body and both their excess and deficiency exert effect on almost all bodily processes. A substantial proportion of people with thyroid pathology observed in the last decade in the regions with unfavorable ecological situation makes correction of existing and search of new ways of thyroid disease treatment vitally important.

To solve the problem, a relationship between the thyroid gland and centers regulating its activity has to be studied first. In this respect, the pineal gland hormones are of particular interest. Their role in initiation and development of thyroid gland disfunction as well as a possibility of using pineal hormones agents have not gained wide recognition in medical practice yet.

Experimental and clinical investigations of direct and reverse bonds in the pineal-thyroid glands system carried out in our laboratory during last years have demonstrated that:

_ thyroid gland is under control of both hypothalamo-pituitarial complex ( by thyrotropin-releasing hormone and thyrotropin ) stimulating production and exertion of thyroxin and triiodothyronine into blood by thyroid gland during daylight hours and pineal gland with its main hormonal product, melatonin, which inhibits synthesis and secretion of thyroid hormones at night. It should be noted that melatonin can act on thyroid gland either directly or via hypothalamo-pituitarial complex;

_ effects of pineal indoles in respect to hypothalamo-pituitarial system of rats show seasonal variations and depend on initial functional state of thyroid gland: melatonin and other methoxiindoles can be powerful inhibitors as well as weak activators of thyroid gland functional activity;

_ antithyroid action of pineal peptides (epithalamin) is weak. It is followed by enhanced compensatory thyroxin deiodination at peripheries and is not dependent on seasonal changes but influences the daytime thyroid hormones rhythms in rat blood serum;

_ in their turn, thyroid hormones also affect pineal gland activity: their excess speeds up and their deficiency slows down biosynthesis and secretion of melatonin. Their stimulating effect on melatonin-producing function of the gland depends on the daylight duration with its maximum in summer and minimum in winter;

_ thyrotropin-releasing hormone of hypothalamus and thyrotropin of pituitary are involved indirectly in melatonin biosynthesis and secretion through stimulation of intrathyroidal hormonogenesis;

_ there exists an ultrashort bond between pineal indoles and peptides at the level of pinealocytes which actively capture exogenic melatonin that results in inhibition of endogenic melatonin production and stimulation of pineal peptides synthesis;

_ dose-dependent inhibitory effect of melatonin in vitro on functional activity of human thyroid gland is realized through its antioxidative action.

Based on the investigations carried out, new pharmacological approaches have been developed to treat thyroid diseases (hyperthyroidism, autoimmune thyroiditis) and related metabolic disorders using the pineal indoles and peptides agents that is a very promising direction not only in thyropathy treatment but also in pharmacotherapy of endocrine diseases as a whole.