Involvement of calcitonin gene-related peptide in elevation of skin temperature in castrated male rats

Abstract

Objectives To assess the involvement of calcitonin gene-related peptide (CGRP) in the occurrence of hot flashes in men after castration for treatment of prostate cancer, we investigated the effects of CGRP on skin temperature in surgically and medically castrated male rats. Methods Changes in skin temperature of the hind paws after intravenous injection of 10 μg/kg of CGRP and CGRP family peptides (adrenomedullin and amylin) were measured at 5-minute intervals for 120 minutes, 3 weeks after bilateral orchiectomy or 2 weeks after subcutaneous injection of a gonadotropin-releasing hormone analogue (1.0 mg/kg Leuplin) in male rats. Antagonism with CGRP 8-37 (1000 μg/kg intravenously), a CGRP 1 receptor antagonist, to the CGRP-induced response was examined by injecting it 10 minutes before injection of CGRP. The effect of testosterone replacement on castration was evaluated in each castrated rat by the administration of testosterone (1.0 mg/kg subcutaneously once a day) for 14 days before the day of the temperature analysis. Results CGRP, but not adrenomedullin and amylin, elevated the skin temperature in surgical or medical castration-induced testosterone-deficient rats more than in the sham-treated rats. The difference was statistically significant. The CGRP-induced potentiation in the castrated rats was inhibited by pretreating with CGRP 8-37 or by supplying testosterone. Conclusions CGRP is the most potent peptide in a family that elevates the skin temperature in male rats. The elevation of the skin temperature was more affected by the testosterone deficiency resulting from castration. These results suggest that CGRP is involved in the mechanism underlying hot flashes in men.