Sex differences in the expression of serotonin-synthesizing enzymes in mouse trigeminal ganglia

Abstract

Migraine headaches are more prevalent in women and often occur during the early phases of the menstrual cycle, implying a link between migraine and ovarian steroids. Serotonin (5-HT) and its receptors have been proposed to play a key role in the pathophysiology of migraine. The trigeminal ganglion (TG) has been proposed as a site for 5-HT synthesis based on the expression of the rate limiting enzyme in peripheral 5-HT synthesis, tryptophan hydroxylase 1 (TPH1), in female rodent trigeminal ganglia. Tryptophan hydroxylase levels vary over the estrus cycle, however, the expression and potential regulation of other enzymes involved in 5-HT synthesis has not been reported in this tissue. C57/BL6 mice of both sexes expressed TPH1 and aromatic amino acid decarboxylase (AADC), the key enzymes involved in 5-HT synthesis. Levels of both enzymes were significantly higher in juvenile males compared with females. In naturally cycling females TPH1 and AADC expression was highest during proestrus when compared with the other phases of the cycle, and this regulation was mirrored at the mRNA level. In situ hybridization experiments detected TPH1 and AADC mRNA in presumptive neurons in the trigeminal ganglion. Both key enzymes involved in the synthesis of 5-HT are expressed in mouse trigeminal ganglion and are localized to neurons. The levels of these enzymes are dependent on gender and estrus cycle stage, suggesting that ovarian steroids might play a role in the regulation of sensory neuron 5-HT synthesis.