Estrogen receptor alpha in giant cell arteritis: A molecular genetic study

Objective Giant cell arteritis (GCA) predominantly affects postmenopausal w omen. Estrogen receptor alpha (ER alpha) accumulates in the cytoplasm of sm ooth muscle cells, activated mononuclear inflammatory cells and giant cells in the temporal arteries of GCA patients, as well as in smooth muscle cell s in arteries from non-GCA controls. The aim of this study was to analyse w hether this accumulation is related to structural aberrations in the ERa mR NA leading to a change in protein structure. Methods Total RNA was extracted from inflamed temporal artery tissue in two GCA patients and from non-inflamed arteries in two non-GCA controls. Produ cts from the nested RT-PCR of the cDNA were cloned and plasmin inserts of 2 0 different clones from each case were investigated using nucleotide sequen ce analysis. Results A total of eight different types of transcripts lacking parts of th e ER alpha mRNA were detected Seven of these could be explained by alternat ive splicing. There were no significant differences between the GCA patient s and the non-GCA controls in terms of the number of transcript variants. Conclusion The accumulated cytoplasmic ER alpha in temporal arterial tissue from elderly persons appears mainly to be of wild Type. The main structura l changes in the ERa mRNA mar be due to alternative splicing. Somatic mutat ions of the ER alpha gene appear to be rare and it is therefore unlikely th at they are involved in the pathogenesis of GCA.