Antiprogestins as a model for progesterone withdrawal.
The key physiological function of the endometrium is preparation for implantation; and in the absence of pregnancy, menstruation and repair. The withdrawal of progesterone is the initiating factor for breakdown of the endometrium. The modulation of sex steroid expression and function with pharmacological agents has provided an invaluable tool for studying the functional responses of the endometrium to sex steroids and their withdrawal. By administration of the antiprogestin mifepristone, it is possible to mimic progesterone withdrawal and study local events in early pregnancy decidua that may play a role in the process of early pregnancy failure. Our data indicate that antagonism of progesterone action at the receptor level results in an up-regulation of key local inflammatory mediators, including NF-kappaB, interleukin-8 (IL-8), monocyte chemotactic peptide-1 (MCP-1), cyclooxygenase 2 (COX-2) and others in decidua. Bleeding induced by mifepristone in the mid-luteal phase of the cycle is associated with changes in the endometrium similar to those that precede spontaneous menstruation including up-regulation of COX-2 and down-regulation of PGDH. Administration of antagonists of progesterone provide an excellent model to study the mechanisms involved in spontaneous and induced abortion as well as providing information which may help devise strategies for treating breakthrough bleeding associated with hormonal contraception.
Critchley
Hilary O D
HO
Obstetrics and Gynaecology, Centre for Reproductive Biology, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, Scotland, UK. hilary.critchley@ed.ac.uk
Kelly
Rodney W
RW
Brenner
Robert M
RM
Baird
David T
DT
D003656:Decidua / Q000187:drug effects; D010064:Embryo Implantation; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D008183:Luteal Phase; D008598:Menstruation / Q000187:drug effects; D015735:Mifepristone / Q000494:pharmacology; D008954:Models, Biological; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism*; D011372:Progestins / Q000037:antagonists & inhibitors*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D015854:Up-Regulation
D006727:Hormone Antagonists; D011372:Progestins; D015735:Mifepristone; D011374:Progesterone; D040262:Receptors, Vascular Endothelial Growth Factor