Linked Life Data

11108885

Source:http://linkedlifedata.com/resource/pubmed/id/11108885

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10-11
pubmed:dateCreated
2000-12-18
pubmed:abstractText
Progesterone antagonists (PAs, antiprogestins) can modulate estrogenic effects in various estrogen-dependent tissues. These modulatory effects are complex and depend on species, tissue, type of compound, dose, and duration of treatment. In non-human primates, PAs, including mifepristone, ZK 137 316 and ZK 230 211, inhibit endometrial proliferation and induce amenorrhea. When administered chronically at relatively low doses, these compounds block the mitotic activity of endometrial epithelium and induce stromal compaction in a dose-dependent manner in both spayed and intact monkeys at high estradiol concentrations. These effects were accompanied by an atrophy of spiral arteries. The antiproliferative effects were endometrium-specific, since the estrogenic effects in the oviduct and vagina were not inhibited by PAs. Similar endometrial antiproliferative effects were also found after treatment with the progesterone receptor modulator (PRM), mesoprogestin J1042. The endometrial antiproliferative effects of PAs, particularly within the endometrial glands, were also observed in spayed rabbits. In spayed rats, however, the PAs did not inhibit, but rather enhanced, various estrogen responses, including endometrial proliferation, pointing to species-specific differences. In conclusion, our studies indicate that both pure PAs and PRMs selectively inhibit estrogen-dependent endometrial proliferation in the primate endometrium without affecting estrogenic response in other estrogen-dependent tissues or inducing unscheduled bleeding. Our studies indicate that the spiral arteries, which are unique to the primate endometrium, are the primary targets that are damaged or inhibited by PAs and PRMs. The damage to these unique vessels may underlay the paradoxical, endometrium-specific, antiproliferative effects of these compounds. Hence, the properties of PAs and PRMs (mesoprogestins) open up new applications in gynecological therapy and hormone replacement therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0039-128X
pubmed:author
pubmed:issnType
Print
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
741-51
pubmed:dateRevised
2005-11-16
pubmed:meshHeading
pubmed:articleTitle
Antiproliferative effects of progesterone antagonists and progesterone receptor modulators on the endometrium.
pubmed:affiliation
Jenapharm GmbH & Co. KG, Otto-Schott-Strasse 15, 077545, Jena, Germany.KristoflChwalisz@Jenapharma.DE
pubmed:publicationType
Journal Article, Review