Sex and female-cycle differences in the expression of the CGRP and amylin family of peptides and receptors in the rat trigeminovascular system
Editor’s note: The research described below comes from a recipient of a 2026 MSC Travel Grant supporting travel to the 11th International CGRP Family Peptides Conference (April 8-10th, 2026, Zurich, Switzerland). These grants reimburse travel expenses for those who have had their abstract for a presentation or poster accepted at a meeting.
By Tayla Rees, PhD, University of Birmingham, UK.
What is the research gap that your study addresses?
Migraine affects more than one billion people worldwide, of whom 75% are women. Migraine is intrinsically linked to changes in female sex hormones throughout a woman’s life, which is most evident during menstruation, with attacks that are more frequent, severe, and resistant to existing treatments, representing a substantial unmet clinical need. Calcitonin gene-related peptide (CGRP), amylin, and their receptors have been linked to migraine. This study aimed to profile the expression of the CGRP peptide and receptor family in the trigeminovascular system, making comparisons between males and females and across the female cycle.
What is your research hypothesis?
There are differences in the expression of the CGRP family of peptides and receptors between males and females and across the female the cycle
What methodology did you use to address your research hypothesis?
Two components of the trigeminovascular system were dissected from eleven total Sprague Dawley rats (3 male, 8 female, 8-12 weeks), the trigeminal ganglia (TG) and the trigeminocervical component (TCC), representing the peripheral and central portions of the trigeminovascular system. Vaginal cytology was used to confirm the rodent cycle (oestrus) stage. RNA was extracted from the tissues, converted to cDNA libraries and the expression of the CGRP peptide and receptor family was quantified using quantitative PCR (qPCR).
What are the main results of your study?
The two CGRP isoforms and amylin were more highly expressed in the TG, whereas the CGRP and amylin receptor subunits were more highly expressed in the TCC. βCGRP and the amylin receptor subunit were significantly more expressed in the TG of female rats than in male rats. This was primarily driven by greater βCGRP and the amylin receptor subunit expression during oestrus, which most closely hormonally aligns with human menstruation, compared to metoestrus, dioestrus and proestrus, which most closely align with the follicular phase.
What conclusions did you reach based on your results?
There are tissue, sex, and oestrus cycle stage-specific mRNA expression patterns of the CGRP peptide and receptor family in rats. These findings support the idea that hormonal fluctuations can influence CGRP biology.
What are the limitations of your study?
The rodent female cycle is 4 days compared to the 28-day human cycle. Although there are similar changes in female sex hormones across both species, the time-scale differences could differentially influence expression. Therefore, similar studies need to be performed in human tissues or cells on modelling the 28-day cycle. Additionally, the rats are “healthy,” and the interaction between female sex hormones and expression of these receptors might be different in a chronic pain context.
What is the relevance of your study to migraine?
It is currently unclear why more women experience migraine than men. Additionally, it is poorly understood why migraine attacks worsen in the peri-menstrual period, and existing treatments have limited efficacy. Therefore, understanding the interaction between female sex hormones and the neuropeptides/receptors involved in migraine will provide insights that can be therapeutically exploited to improve patient outcomes.