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

Christopher S. Keator, Kuni Mah, Lindsay Ohm, Ov D. Slayden

    Research output: Contribution to journalArticle

    12 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)1715-1728
    Number of pages14
    JournalHuman Reproduction
    Volume26
    Issue number7
    DOIs
    StatePublished - Jul 2011

    Keywords

    • endometrium
    • endothelin
    • macaque
    • menstrual cycle
    • ovarian hormones

    ASJC Scopus subject areas

    • Reproductive Medicine
    • Obstetrics and Gynecology

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