Intranasal and Intramuscular Administration of Lysine-Palmitoylated Peptide 612–627 of Thyroid-Stimulating Hormone Receptor Increases the Level of Thyroid Hormones in Rats

Abstract

Nowadays, a search of new regulators of the hypothalamic-pituitary-thyroid (HPT) axis is a very actual problem, and one of the promising approaches to it is designing lipid-modified peptides corresponding to intracellular loops of thyroid-stimulating hormone receptor (TSHR). The aim of the present work was, first, to study the influence of single and 3-day treatment of rats with intranasally (i.n.) and intramuscularly (i.m.) administered lysine-palmitoylated peptide 612–627-K(Pal)A corresponding to the third intracellular loop of rat TSHR on the levels of thyroid hormones and TSH, and, second, the influence of peptide treatment on the sensitivity of HPT axis to thyroliberin. A single and 3-day treatment with i.n. peptide 612–627-K(Pal)A at a daily dose 450 μg/kg significantly increased fT4, tT4 and tT3 levels. i.m. peptide 612–627-K(Pal)A at a daily dose 900 μg/kg increased fT4 level, but influenced tT4 and tT3 levels not very significantly. Concerning 3-day treatment, the stimulating effect of the peptide on production of thyroid hormones was reduced on the last day due to decreased sensitivity of the thyroid to peptide. This was evidenced by weakening of stimulating influence of thyroliberin on production of thyroid hormones in rats treated for 2 days with 612–627-K(Pal)A. Unmodified peptide 612–627-KA, taken for comparison, had no influence on the thyroid hormonal status at the doses effective with the palmitoylated analog. Thus, peptide 612–627-K(Pal)A effectively stimulated production of thyroid hormones, so that there are all reasons to regard it as a prototype for creating the novel thyroid regulators.