Mineralocorticoid Receptor in the Primate Endometrium Throughout the Menstrual Cycle [5F]

INTRODUCTION: Throughout the menstrual cycle, the endometrium undergoes morphological and biochemical changes reflecting ovarian hormone secretion. These changes are associated with specific receptors located throughout the endometrial tissue. Alongside receptors for ovarian hormones, the human endometrium contains all of the elements of renin-angiotensin-aldosterone system (RAAS). Given certain progestins play a role in RAAS modulation through anti-mineralocorticoid properties, we believe that the mineralocorticoid receptor (MR) has a significant role in the menstrual cycle and potentially in abnormal uterine bleeding (AUB). METHODS: Full-thickness uterine samples were obtained from adult female rhesus macaques during an artificial menstrual cycle controlled with estrogen (E) and progestin (P) implants at 3 separate points: menstrual (E-3P), proliferative (14dE) and secretory (E+5P). Tissue sections were immunohistochemically stained and evaluated under bright microscopy. ImageJ analysis software was used to analyze vasculature for integrated density and area fraction. RESULTS: MR is present in the endometrial endothelial cells during all three phases of the menstrual cycle in rhesus macaques. The percent area was 25.54% in the proliferative phase, 18.86% in the menstrual phase, 17.34% in the secretory phase. CONCLUSION: MR has been identified for the first time to our knowledge within the endometrial endothelial cells. Given the anti-mineralocorticoid properties of certain progestins used for contraception and their association with amenorrhea or AUB, MR antagonism specifically may explain these changes. In select patient populations, such as obese females at increased risk for hypertension and elevated aldosterone activity, the increased incidence of amenorrhea on certain progestin-only contraceptives may be related to higher degree of anti-RAAS activity within the endometrium.