THE STUDY OF DOSEDEPENDENCY OF THE STIMULATING EFFECT OF PEPTIDE DERIVED FROM THYROTROPIN HORMONE RECEPTOR ON PRODUCTION OF THYROID HORMONES IN RATS
Background. Search and development of new regulators of functional activity of the hypothalamic- pituitary-thyroid axis is one of actual problems in endocrinology and pharmacology. We have previously shown that palmitoylated peptide 612-627 (Pal) structurally corresponding to the third intracellular loop of receptor of thyroid-stimulating hormone (TSH) activates the adenylyl cyclase signaling system in thyroidal membranes in vitro and stimulates the production of thyroxine by the thyroid gland in vivo. Objective. The aim of this work was to study a dose-dependency of the stimulating effect of peptide 612-627 (Pal) on the level of thyroid hormones in its intranasal and intramuscular administration into rats. Design and methods. The peptide was administered once to Wistar male rats at the doses from 45 to 900 pg/kg when administered intranasally and at the doses from 150 to 1350 pg/kg when administered intramuscularly. Prior to administration and for 6 h after administration the changes of the levels of free (fT<sub>4</sub>) and total thyroxine (tT<sub>4</sub>) and total triiodothyronine (tT<sub>3</sub>) were evaluated. Results. It is shown that peptide 612-627 (Pal) in both routes of administration in a dose- dependent manner increased the levels of fT<sub>4</sub> and tT<sub>3</sub> At the same time, the intranasal route was more effective as ED<sub>50</sub> value and the maximal stimulating effect on fT<sub>4</sub> production when peptide administered intranasally was 87 pg/kg and 38 %, while in the case of intramuscular route - 275 pg/kg and 25 %, respectively. Conclusion. These findings indicate the ability of peptide 612-627 (Pal) to effectively stimulate hormone-producing function of the thyroid gland when peptide administered intranasally into rats at the range of the doses 225-450 pg/kg.