The effect of ۱۷β-estradiol on gene expression of calcitonin gene-related peptide and some pro-inflammatory mediators in peripheral blood mononuclear cells from patients with pure menstrual migraine

Objective(s):The neuropeptide calcitonin gene-related peptide (CGRP) has long been postulated to play an integral role in the pathophysiology of migraine. Earlier studies showed that CGRP can stimulate the synthesis and release of nitric oxide (NO) and cytokines from trigeminal ganglion glial cells. The purpose of this study was to determine the effect of ۱۷β-estradiol in regulation of CGRP expression, inducible nitric oxide synthase (iNOS) activity, and NO and interleukin-۱beta (IL-۱β) release in cultured peripheral blood mononuclear cells (PBMCs) from patients with pure menstrual migraine and healthy individuals. Materials and Methods: This study was performed on twelve patients with pure menstrual migraine and twelve age-and sex-matched healthy individuals. PBMCs treated with ۱۷β-estradiol for ۲۴ hr at physiological and pharmacological doses. Gene expression was evaluated by real time-PCR. CGRP and IL-۱β proteins in culture supernatant were determined by ELISA method. Activity of iNOS in PBMCs and total nitrite in the culture supernatant were measured by colorimetric assays. Results:Treatment with ۱۷β-estradiol had a biphasic effect on expression of CGRP. We found that ۱۷β-estradiol treatment at pharmacological dose significantly increases mRNA expression of CGRP in both groups (P<۰.۰۰۱), whereas at physiological dose it could significantly decrease CGRP mRNA expression (P<۰.۰۰۱), CGRP protein levels, IL-۱β release, NO production and iNOS activity only in patient groups (P<۰.۰۵). Conclusion:Collectively, it appears that ۱۷β-estradiol can exert protective effect on decrease of inflammation in migraine via decrease in levels of CGRP, IL-۱β and iNOS activity; however, more studies are necessary in this regard.

کلیدواژه ها:

Calcitonin gene-related- peptide ، Inducible nitric oxide-synthase ، Neurogenic inflammation ، Nitric oxide ، Pure menstrual migraine ، ۱۷β-estradiol