Linked Life Data

21558311

Source:http://linkedlifedata.com/resource/pubmed/id/21558311

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2011-6-23
pubmed:abstractText
After menstruation, the endometrium has a remarkable capacity for repair, but the factors involved remain undefined. We hypothesize adrenomedullin (AM) plays a role in this process. Premenstrually progesterone levels decline, stimulating prostaglandin (PG) synthesis, vasoconstriction, and hypoxia. This study aimed to determine 1) AM expression throughout the menstrual (M) cycle and 2) its regulation by PG and hypoxia. Human endometrial biopsies (n = 51) were collected with ethical approval and consent. AM mRNA expression was examined by quantitative RT-PCR and was found to be selectively elevated in endometrium from the menstrual (M) phase (P < 0.001). AM immunohistochemical staining was maximal in M and proliferative (P) endometrium. Culture of secretory, but not P, explants with 100 nm PGF(2?) or hypoxia (0.5% O2) increased AM mRNA (P < 0.05). P explants were induced to increase AM expression using in vitro progesterone withdrawal but required the presence of hypoxia (P < 0.05). Short hairpin sequences against hypoxia-inducible factor-1? (HIF-1?) inhibited AM hypoxic up-regulation but did not alter PGF(2?)-induced expression. The AM receptor was immunolocalized to endothelial cells in both lymphatic and blood vessels. Conditioned medium from PGF(2?)-treated cells increased endothelial cell proliferation and branching (P < 0.05). This was abolished by AM receptor antagonists. In conclusion, AM is elevated at the time of endometrial repair and induces both angiogenesis and lymphangiogenesis by stimulating endothelial cell proliferation and tube formation. In the human endometrium, AM expression is up-regulated by two mechanisms: a HIF-1?-mediated hypoxic induction and a HIF-1?-independent PGF(2?) pathway. These physiological mechanisms may provide novel therapeutic targets for disorders such as heavy menstrual bleeding.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1945-7170
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
152
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2845-56
pubmed:dateRevised
2011-10-13
pubmed:meshHeading
pubmed-meshheading:21558311-Adrenomedullin, pubmed-meshheading:21558311-Adult, pubmed-meshheading:21558311-Angiogenesis Inducing Agents, pubmed-meshheading:21558311-Cell Hypoxia, pubmed-meshheading:21558311-Cell Line, pubmed-meshheading:21558311-Cell Proliferation, pubmed-meshheading:21558311-Dinoprost, pubmed-meshheading:21558311-Endometrium, pubmed-meshheading:21558311-Endothelium, Vascular, pubmed-meshheading:21558311-Female, pubmed-meshheading:21558311-Gene Expression Regulation, pubmed-meshheading:21558311-Gene Silencing, pubmed-meshheading:21558311-Humans, pubmed-meshheading:21558311-Hypoxia-Inducible Factor 1, pubmed-meshheading:21558311-Lymphangiogenesis, pubmed-meshheading:21558311-Menstrual Cycle, pubmed-meshheading:21558311-Middle Aged, pubmed-meshheading:21558311-Organ Culture Techniques, pubmed-meshheading:21558311-RNA, Messenger, pubmed-meshheading:21558311-RNA, Small Interfering, pubmed-meshheading:21558311-Receptors, Adrenomedullin, pubmed-meshheading:21558311-Receptors, Prostaglandin
pubmed:year
2011
pubmed:articleTitle
The expression and regulation of adrenomedullin in the human endometrium: a candidate for endometrial repair.
pubmed:affiliation
Centre for Reproductive Biology, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't