DARU Journal of Pharmaceutical Sciences 2009. 17(2):109-112.

The effects of interaction between ghrelin and substance-P on mean plasma thyroid hormones concentration and body weight
H Khazali , F Mahmoudi


Background and the purpose of the study: Ghrelin increases food intakes and body weight via growth hormone secretagogues receptor (GHSR-Ia). [D-Arg-1, D-phe-5, D-Trp-7,9, Leu-11]Substance-P (an analog of Substance-P) is known as an antagonist of GHSR-Ia receptor which inhibits ghrelin- induced food intakes. Thyroid hormones have also an important role in the regulation of metabolism and body weight. The goal of this study was to determine the effect of different doses of either ghrelin, analog of Substance-P or their interactions on the body weight, mean plasma TSH, Triiodothyronine (T3) and Thyroxine (T4) concentration and to investigate whether ghrelin exerts its effects on thyroid axis activity via GHSR-Ia.

Methods: Rats received different doses of ghrelin (1, 5, or 10 nmol), analog of Substance P (5, 10, 20 nmol) or saline via lateral cerebral ventricle. Body weight was measured daily before injectionand at 9 h of the day after the final injection. The blood samples were collected at the end of experiment. Plasma was assayed for thyroid hormones concentration.

Results: Ghrelin significantly increased body weight and decreased mean plasma TSH, T3 and T4 concentrations in a dose related manner. Analog of Substance-P significantly decreased body weight and increased thyroid hormones concentration in a dose related manner. It blocked the stimulatory effect of ghrelin on body weight and the inhibitory effect of ghrelin on thyroid axis activity.

Conclusion: From the results of this study it appears that analog of substance P may be useful for treatment of obesity.


Ghrelin, Substance-P, Triiodothyronine (T3), Thyroxine (T4),

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