Effects of estrogen on the serotonergic system and calcitonin gene-related peptide in trigeminal ganglia of rats

BACKGROUND The prevalence of migraine is 3-folds higher in females than in males, and it is intricately related to the levels of estrogen. Estrogen may regulate the expression of metabolic enzymes and receptors of serotonin and also calcitonin gene-related peptide (CGRP), which are implicated in migraine pathogenesis. PURPOSE To study the effects of estrogen on the components of serotonin system and CGRP in trigeminal ganglia of ovariectomized (OVX) rats. METHODS OVX rats were administered estrogen in silastic tubes and after 48 h, serum estrogen levels were determined. Trigeminal ganglia tissues were used for RT-PCRs of tryptophan hydroxylase (TPH), monoamine oxidase (MAO), serotonin receptors (5-HT1A, 5-HT1B, 5-HT2A), estrogen receptor (ER) and CGRP. Western blots of TPH and MAO were performed. RESULTS Estradiol administration to OVX rats increased TPH mRNA levels, while decreased MAO mRNA levels in trigeminal ganglia tissue. Western blot data correlate with the gene expression results. The decreased mRNA levels of serotonin receptors following ovariectomy were restored in estrogen-replenished rats. The induced gene expression of ER in OVX rats was restored following estrogen replenishment. CONCLUSION Estrogen levels affect the levels of serotonin metabolizing enzymes and its receptors besides CGRP levels. Since TPH and MAO levels regulate circulating and physiologically available serotonin content, the regulation of serotonin metabolizing enzymes suggest a plausible mechanism by which estrogen alleviates migraine in women.