Melatonin receptors and their role in endometrial cell proliferation

Eutopic endometrium and endometriosis contain melatonin receptors

Key Points

Highlights:

• The presence of melatonin receptors in human eutopic endometrium, endometriomas, and peritoneal lesions and the evidence of melatonin activity in endometrial epithelial cell proliferation demonstrate that melatonin may be a good alternative in the treatment of endometriosis.  

Importance:

• The demonstration of melatonin activity in endometrial epithelial cell proliferation indicates that melatonin may be hope for the management of endometriosis.

 What’s done here?

• This single-center basic science study was conducted at McMaster University Medical Centre.
• Women above 18 years of age who underwent an operation for suspected endometriosis, pelvic pain, and fertility care were included.
• Pregnancy, malignancy, infection, systemic autoimmune disease, adenomyosis or hormonal therapy were the reasons for exclusion from the study.
• The demographic and clinical characteristics were recorded including menstrual cycle length, last menstrual period and pelvic pain.
• Three categories were endometriosis, peritoneal endometriosis, and the control group having no endometriosis, all histopathologically confirmed.
• Eutopic endometrium and endometriotic lesions were evaluated for melatonin receptor status by immunohistochemistry.

Key results:

• A total of 46 women [31 women in the case group (20 with endometrioma only, 11 with peritoneal endometriosis only), 15 women in the control group] were included.
• No statistically significant differences found between groups in terms of mean age, duration of bleeding, ethnicity, occupational and smoking status.
• The expression of melatonin receptors in epithelial cells across the menstrual cycle was shown by immunohistochemical staining.
• Melatonin receptors 1A and 1B mRNA was expressed predominantly in peritoneal endometriotic lesions, whereas these lesions expressed significantly decreased MRIB protein expression comparing to endometriomas and eutopic endometrium.
• After 48 hours of culture, the combination of melatonin and estradiol significantly increased estradiol-induced endometrial epithelial cell proliferation. However, melatonin alone did not affect endometrial epithelial cell proliferation after this period of culture.

Lay Summary

Women with endometriosis demand therapy for the most common symptoms, which are pelvic pain and infertility. Despite extensive research, the exact pathophysiological mechanism and the optimal management of endometriosis still remains unclear. Management of endometriosis should aim to relieve pain, ameliorate infertility and improve quality of life.

Current medical and surgical treatment options have several limitations including the side effects, costs, the risk of recurrence, and effects on conception capability. The benefit of melatonin, which is a hormone produced by the pineal gland, in the treatment of endometriosis has already been demonstrated in animal experiments. Mosher et al, a group of scientists from Canada and the United States, published a study titled as “Melatonin activity and receptor expression in endometrial tissue and endometriosis” in the journal named "Human Reproduction".

The authors sought to investigate the expression of melatonin receptors in endometriomas, peritoneal endometriotic lesions, and eutopic endometrium. They also evaluated the effect of melatonin in the endometrial epithelial cell proliferation in vitro.

Women with the planned operation for suspected endometriosis, pelvic pain, and fertility care were included and they were divided into three groups as patients with endometrioma, patients with peritoneal lesions and patients without endometriosis, the latter as the control group. The diagnosis of endometriosis was confirmed by the histopathological examination. There were no demographic differences between the patients included in the study.

They documented significantly increased melatonin receptor mRNA expression and significantly decreased receptor 1B protein expression in peritoneal endometriotic lesions compared to endometriomas and eutopic endometrium. After 48 hours of culture, the combination of melatonin and estradiol significantly increased estradiol-induced endometrial epithelial cell proliferation. However, only melatonin application did not affect endometrial epithelial cell proliferation after this period of culture.

The authors suggested that melatonin may be used as an adjunct in the management of endometriosis. “Melatonin treatment, at all concentrations tested, inhibited estradiol-induced endometrial epithelial cell proliferation,” they added.  

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/31211323