Endocrine Abstracts

Background: The melanocortin system is known to be involved in hypothalamic regulation of energy balance, which is implicated in reproductive success. However, the peripheral role for melanocortin receptor (MCR) signalling in the reproductive system has not been described. During a clinical trial of repeated high dose tetracosactide (ACTH_1–24) injection, four of nine premenopausal women with Addison’s disease developed menstrual disturbances. We wondered if these adverse effects were mediated via direct melanocortin signalling in human endometrium, which has not been previously examined.

Methods: Endometrial (n=8) biopsies were obtained from pre-menopausal women after hysterectomy for non-endometrial pathology. Decidual (8–10 weeks gestation; n=5) tissues were obtained after termination of apparently normal pregnancies. The localisation of the expression of melanocortin receptors (MCR 1-5) in the human endometrium was performed using immunocytochemistry. Tissue culture was used to characterise the effects of ACTH_1–24 on decidual tissue and blood vessel integrity determined by immunostaining for vascular smooth muscle cell (VSMC) markers.

Results: Robust expression of MC5R was demonstrated in human endometrium. Moderate to strong MC2R and MC3R expressions were also shown in this tissue. Expression of MC1R and MC4R was negligible. A dose-dependent reduction in VSMC in the cultured decidual tissue’s vessel wall was observed during treatment with high concentrations of ACTH_1–24. However, the difference was only significant after treatment with the highest concentration of ACTH (500 ng/ml) (P=0.03).

Conclusion: Our study demonstrated for the first time MC2R, MC3R and MC5R expression in human endometrium at the protein level. These melanocortin receptors may play a role in regulating endometrial proliferation or integrity, which could mediate menstrual disturbances observed in the clinical trial. Understanding of melanocortin receptors’ role in the uterus and decidual tissue could potentially inform the pathogenesis of uterine dysfunction. The effects of ACTH excess or deficiency on the endometrium via melanocortin signalling should also be explored further.