The effect of various doses of mifepristone on endometrial leukaemia inhibitory factor expression in the midluteal phase--an immunohistochemical study.
Leukaemia inhibitory factor (LIF) is a cytokine which plays an obligatory role in mouse blastocyst implantation. In human endometrium, LIF expression is significantly increased in the mid-luteal phase indicating that LIF may also play an important role in the human. We have previously shown that a single dose of 200 mg of mifepristone immediately post-ovulation is an effective contraceptive method, probably due to inhibition of endometrial development and function. The purpose of this study was to investigate the effect of various doses of mifepristone on endometrial LIF expression. A total of 22 fertile, regularly-menstruating women were studied during control and treatment cycles. The subjects were divided into four groups: group I received a single dose of 200 mg of mifepristone on cycle day LH + 2 (n = 7). The subjects in groups II and III were treated with either 5 mg (n = 5) or 2.5 mg (n = 5) once a week for 2 months. Group IV subjects received 0.5 mg per day (n = 5) of mifepristone for 3 months. LIF was measured immunohistochemically in endometrial tissue specimens taken on the corresponding day (cycle day LH + 6 to LH + 8) in hormonally-characterized control and treatment cycles. LIF immunostaining was observed in all controls and located to the cytoplasm of the luminal and glandular epithelial cells and stromal cells. In the treatment cycles the staining of luminal epithelium and stroma was similar to controls, while the glandular staining was reduced in all treatment groups. This study reveals that early luteal phase treatment as well as intermittent or daily low dose treatment with mifepristone reduces endometrial glandular LIF expression at the expected time of implantation. The results further support the contraceptive potential of mifepristone in low doses.
Danielsson
K G
KG
Department of Woman and Child Health, Karolinska Hospital, Stockholm, Sweden.
Swahn
M L
ML
Bygdeman
M
M
D000328:Adult; D000818:Animals; D003271:Contraceptive Agents, Female / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation / Q000187:drug effects; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D006131:Growth Inhibitors / Q000378:metabolism*; D006727:Hormone Antagonists / Q000008:administration & dosage*; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008183:Luteal Phase / Q000187:drug effects* / Q000378:metabolism*; D008186:Luteolytic Agents / Q000008:administration & dosage; D008222:Lymphokines / Q000378:metabolism*; D051379:Mice; D015735:Mifepristone / Q000008:administration & dosage*; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors
D003271:Contraceptive Agents, Female; D006131:Growth Inhibitors; D006727:Hormone Antagonists; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008186:Luteolytic Agents; D008222:Lymphokines; D011980:Receptors, Progesterone; D015735:Mifepristone