title: The effect of 17β-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.
abstract: OBJECTIVE
  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 17β-estradiol in regulation of CGRP expression, inducible nitric oxide synthase (iNOS) activity, and NO and interleukin-1beta (IL-1β) release in cultured peripheral blood mononuclear cells (PBMCs) from patients with pure menstrual migraine and healthy individuals.
  
  
  METHODS
  This study was performed on twelve patients with pure menstrual migraine and twelve age-and sex-matched healthy individuals. PBMCs treated with 17β-estradiol for 24 hr at physiological and pharmacological doses. Gene expression was evaluated by real time-PCR. CGRP and IL-1β 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 17β-estradiol had a biphasic effect on expression of CGRP. We found that 17β-estradiol treatment at pharmacological dose significantly increases mRNA expression of CGRP in both groups (P<0.001), whereas at physiological dose it could significantly decrease CGRP mRNA expression (P<0.001), CGRP protein levels, IL-1β release, NO production and iNOS activity only in patient groups (P<0.05).
  
  
  CONCLUSIONS
  Collectively, it appears that 17β-estradiol can exert protective effect on decrease of inflammation in migraine via decrease in levels of CGRP, IL-1β and iNOS activity; however, more studies are necessary in this regard.
authors.affiliation: Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran ; Reference Laboratory, Iranian Social Security Organization, Tehran, Iran.
authors.forename: Azam
authors.initials: A
authors.lastname: Karkhaneh
authors.affiliation: Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ansari
authors.affiliation: Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Solaleh
authors.initials: S
authors.lastname: Emamgholipour
authors.affiliation: High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
authors.forename: Mohammad Hessam
authors.initials: MH
authors.lastname: Rafiee
keywords: 17β-estradiol; Calcitonin gene-related-peptide; Inducible nitric oxide-synthase; Neurogenic inflammation; Nitric oxide; Pure menstrual migraine