Expression of melanocortin receptors in human endometrium.

study questionAre melanocortin receptors (MCR1-5) expressed in the endometrium? SUMMARY ANSWER: MCR1-5 are expressed in endometrium to varying degrees, with MC2R, MC3R and MC5R being the most abundant and the majority of expression being observed in glandular epithelium. WHAT IS KNOWN ALREADY: Women with Addison's disease who were being administered synthetic ACTH reported menstrual complications as a side effect. There is no previous literature on expression of the melanocortin receptors within the endometrium, and therefore whether ACTH may directly affect the endometrial vasculature. STUDY DESIGN, SIZE, DURATION: Endometrial biopsies were taken from hysterectomy specimens in control women without endometrial pathology (n = 4 for each of proliferative and late-secretory phases). Biopsies were formalin fixed and embedded in paraffin wax. Decidual samples (n = 7) were cultured in a range of concentrations of synthetic ACTH for 3 days before being formalin fixed and embedded in paraffin wax. PARTICIPANTS/MATERIALS, SETTING,

methodsEndometrial paraffin embedded sections were immunostained for MCR1-5 and assessed using a modified quickscore with luminal epithelium, glandular epithelium, stromal cells, endothelial cells and vascular smooth muscle cells all being assessed separately. Cultured decidual biopsy paraffin embedded sections were immunostained for H-caldesmon and the number of layers of vascular smooth muscle cells surrounding the vessel assessed. MAIN RESULTS AND THE ROLE OF CHANCE: All five melanocortin receptors were shown to be immunolocalised to the endometrium, with MC5R, MC2R and MC3R being the most abundant and limited immunostaining being observed for MC1R and MC4R. Treatment of decidual biopsies with synthetic adrenocorticotropin (ACTH) resulted in loss of vascular integrity. LIMITATIONS, REASONS FOR CAUTION: This is an observational study and does not definitively demonstrate a link between synthetic ACTH administration and menstrual complications. WIDER IMPLICATIONS OF THE

findingsThis is the first study to demonstrate widespread expression of melanocortin receptors within the endometrium. Further study is required to determine the role of this hormone family in endometrial function. STUDY FUNDING/COMPETING INTERESTS: The work was part funded by MRC grant G09000001. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.