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

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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.

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Abbreviations

AC:

Adenylyl cyclase

fT4 :

Free thyroxine

GPCR:

G protein-coupled receptor

HPT axis:

Hypothalamic-pituitary-thyroid axis

ICL:

Intracellular loop

Pal:

Palmitoyl

PAR:

Protease-activated receptor

PLCβ:

Phospholipase Cβ

tT3 :

Total circulating triiodothyronine

tT4 :

Total circulating thyroxine

TM:

Transmembrane region

TRH:

Thyroid-stimulating hormone-releasing hormone

TSH:

Thyroid-stimulating hormone

TSHR:

Thyroid-stimulating hormone receptor

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Acknowledgments

This work was supported by project No. 14-15-00413 from the Russian Science Foundation. The authors are grateful to Inga Menina for linguistic assistance.

Conflict of interest

Derkach K, Shpakova E, Titov A and Shpakov A declare that they have no conflict of interest.

Statement of Informed Consent

Informed consent was obtained from all individual participants included in the study.

Statement on the Welfare of Animals

The experiments were carried out under the Bioethics Committee of Sechenov Institute of Evolutionary Physiology and Biochemistry, St. Petersburg, Russia (Institutional Guidelines, December 23, 2010) and under the guidelines of the National Institutes of Health Regulations for the Care and Use of Animals for Scientific Purposes according to the criteria outlined in the “Guide for the Care and Use of Laboratory Animals”. All efforts were made to minimize animal suffering and to reduce the number of animals used.

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Thorez av. 44, 194223, St. Petersburg, Russia

    Kira V. Derkach, Alexey K. Titov & Alexander O. Shpakov

  2. Institute of Macromolecular Compounds, Russian Academy of Sciences, Bol’shoi av. 31, 199004, St. Petersburg, Russia

    Elena A. Shpakova

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  1. Kira V. Derkach
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  2. Elena A. Shpakova
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  3. Alexey K. Titov
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  4. Alexander O. Shpakov
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Correspondence to Alexander O. Shpakov.

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Derkach, K.V., Shpakova, E.A., Titov, A.K. et al. Intranasal and Intramuscular Administration of Lysine-Palmitoylated Peptide 612–627 of Thyroid-Stimulating Hormone Receptor Increases the Level of Thyroid Hormones in Rats. Int J Pept Res Ther 21, 249–260 (2015). https://doi.org/10.1007/s10989-014-9452-6

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