Estradiol induces an accumulation of free heparan sulfate glycosaminoglycan chains in uterine epithelium.
Blastocyst implantation in the mouse uterus is triggered by an estrogen surge that induces a number of characteristic changes in biosynthetic activity of the endometrial stroma and epithelium, including a reduction in the thickness of the epithelial plasma membrane coat, immediately preceding attachment of the blastocyst. A brief exposure of the uterine luminal surface to 1% Nonidet-40 (NP-40) nonionic detergent extracted this surface coat along with membrane-associated and soluble [35S]sulfate-labeled proteoglycans specifically from the epithelium. Extraction from the underlying stroma appeared to have been prevented by the epithelial basal lamina, which was minimally affected by 1% NP-40, but was extracted by subsequent treatment with 1% NP-40 in 1 M KCl. About 70-80% of the [35S]sulfate in proteoglycans extracted from the uteri of ovariectomized mice with NP-40 was associated with heparan sulfate proteoglycans that eluted from Sepharose CL-4B in a peak at 0.55 Kd. All remaining radioactivity could be accounted for by dermatan sulfate/chondroitin sulfate proteoglycans. Specifically, in the NP-40 extract of uteri from ovariectomized mature mice and intact immature mice, but not in the culture medium or residual tissue, estradiol induced a pronounced increase in the relative amount of radioactivity in a 0.8 Kd peak, which appeared to contain only free heparan sulfate glycosaminoglycan chains. The same relative increase was seen in the NP-40 extract of uteri from intact 3.5-day pregnant mice. We conclude that estradiol induces cellular changes that result in an increased accumulation of epithelial heparan sulfate proteoglycan degradation product immediately preceding normal attachment of the blastocyst.
D000818:Animals; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006025:Glycosaminoglycans / Q000302:isolation & purification / Q000378:metabolism*; D006497:Heparan Sulfate / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D009924:Organ Culture Techniques; D010052:Ovariectomy; D011247:Pregnancy; D014599:Uterus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D004958:Estradiol; D006025:Glycosaminoglycans; D006497:Heparan Sulfate