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Objective: Our objective was to investigate endometrial expression of Indian Hedgehog (] during the menstrual cycle and the effects of the selective progesterone receptor modulator CDB-2914 on its expression.
Design and Setting: Comparisons between normally cycling volunteers and women with symptomatic fibroids who received CDB-2914 or placebo were made at a clinical research center.
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Progesterone is critical for secretory endometrial differentiation in women, but its downstream mediators are poorly understood.
The temporal increase in endometrial IHH and GLI1 during the secretory phase, and their modulation by CDB-2914, suggests progestin regulation and a potential role in endometrial differentiation and implantation.
In situ hybridization showed IHH m RNA expression in glands and stroma that was stronger in secretory samples.
Similarly, IHH and GLI1 are increased at proestrus and during early pregnancy in the rat (11).
By contrast, estrogen exposure down-regulates expression in the immature rat (7).
Among volunteers, IHH and GLI1 immunohistochemistry scores were higher in the secretory than proliferative phase in the nuclei and cytoplasm of glands and stroma (P=0.0002-0.04).
Compared with follicular-phase controls, women exposed to CDB-2914 showed increased IHH expression in all compartments except stromal cytoplasm (P=0.0199-0.0423); GLI1 was up-regulated in glandular nuclei and cytoplasm compared with both volunteers and women receiving placebo (P≤0.0416).



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