Estrogen and progesterone regulate expression of the endothelins in the rhesus macaque endometrium

• Published in: Human reproduction (Oxford) Vol. 26; no. 7; pp. 1715 - 1728
• Main Authors: Keator, Christopher S., Mah, Kuni, Ohm, Lindsay, Slayden, Ov D.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.07.2011
• Subjects: Animals; Aspartic Acid Endopeptidases - genetics; Aspartic Acid Endopeptidases - metabolism; Biological and medical sciences; Endometrium - cytology; Endometrium - drug effects; Endometrium - metabolism; Endothelin-Converting Enzymes; Endothelins - analysis; Endothelins - genetics; Endothelins - metabolism; Estrogens - pharmacology; Female; Gene Expression Regulation - drug effects; Gynecology. Andrology. Obstetrics; Macaca mulatta - metabolism; Macaca mulatta - physiology; Medical sciences; Menstrual Cycle - drug effects; Menstrual Cycle - metabolism; Menstruation - drug effects; Menstruation - metabolism; Metalloendopeptidases - genetics; Metalloendopeptidases - metabolism; Neprilysin - genetics; Neprilysin - metabolism; Original; Progesterone - pharmacology; Receptors, Endothelin - genetics; Receptors, Endothelin - metabolism; Stromal Cells - metabolism; endometrium; endothelin; ovarian hormones; macaque; menstrual cycle; Endothelin; Menstrual cycle; Estrogen; Monkey; Ovarian hormone; Progestagen; Vertebrata; Regulation(control); Mammalia; Uterus; Female genital system; Primates; Rh-System; Progesterone; Sex steroid hormone; Endometrium
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/der115

BACKGROUND Endothelins (EDNs) are thought to modulate endometrial blood flow during menses, stromal healing and endometrial growth during the proliferative phase. Our goal was to assess the effects of estrogen and progesterone on the EDN paracrine system in the endometrium of rhesus macaques. METHODS In this study, archived samples were used. These samples were collected from oophorectomized rhesus macaques that were treated sequentially with estradiol (E2) and then E2 plus progesterone to create artificial menstrual cycles. Endometrium from animals in the menstrual, proliferative and secretory phases of the artificial cycle were analyzed by real-time PCR, in situ hybridization and immunocytochemistry to detect changes in EDN peptides (EDN1, EDN2, EDN3), EDN receptors (EDNRA, EDNRB), EDN-converting enzyme 1 (ECE1) and membrane metalloendopeptidase (MME)—an enzyme that degrades the EDNs. RESULTS Compared with the late secretory phase, progesterone withdrawal at the end of the artificial menstrual cycle triggered an increase (P< 0.05) in EDN1, EDNRB and ECE1 in the upper functionalis zone during menses of the next cycle. Treatment with E2 alone in the proliferative phase increased (P< 0.05) EDNRA transcript, which was confined predominantly to the stromal cells. E2 plus progesterone in the artificial secretory phase suppressed (P< 0.05) the expression of EDN3 in the functionalis zone stroma and epithelia, tended (P= 0.08) to attenuate levels of epithelial EDN2 and markedly up-regulated (P< 0.05) the stromal expression of MME. CONCLUSIONS Our results indicate that estrogen and progesterone regulate the EDN family during the menstrual cycle. The changes in the EDN paracrine system during the mid-secretory phase may indicate a role for EDN during embryo implantation.