NEW APPROACHES TO ATTACK THYROID GLAND DYSFUNCTION

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NEW APPROACHES TO ATTACK THYROID GLAND DYSFUNCTION

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@... , 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.