Differential effects of ovarian steroids and triphenylethylene compounds on macromolecular uptake and thymidine incorporation in the mouse uterus.
In the rodent uterus, estrogen elicits a biphasic response i.e. an early phase (Phase I) and a late phase (Phase II). Estradiol-17 beta (E2) and estriol (E3), as well as triphenylethylene (TPE) compounds, CI-628 and clomiphene citrate (CC), were used to characterize Phase I and Phase II responses in uterine preparation for implantation in the mouse. While uterine macromolecular uptake (vascular permeability), a Phase I response, was studied in progesterone (P4)-primed animals, uterine [3H]thymidine incorporation (DNA synthesis), a Phase II response, was investigated with and without P4-priming. In the P4-primed uterus, all compounds, except CC, significantly increased uterine macromolecular uptake as determined by interstitial tissue accumulation of [125I]bovine serum albumin [( 125I]BSA). DNA synthesis as determined by cellular incorporation of [3H]thymidine was modulated by P4, estrogens and TPE compounds in a cell-type specific and temporal manner. As a single injection and in the absence of P4, E2 induced [3H]thymidine incorporation in the luminal and glandular epithelium at 18 and 24 h. E3 was inferior to E2 in this response. On the other hand, treatment with P4 for 1 day or 4 days induced [3H]thymidine incorporation primarily in stromal cells. However, stromal cell incorporation was potentiated when P4 treatment was combined with estrogens or TPE compounds. These results reveal the relative importance of Phase I and cell-type specific Phase II responses in uterine preparation for implantation.
Department of Obstetrics/Gynecology and Physiology, University of Kansas Medical Center, Ralph L. Smith Research Center, Kansas City 66103.
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D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002996:Clomiphene / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis*; D004958:Estradiol / Q000494:pharmacology; D004964:Estriol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D051379:Mice; D009594:Nitromifene / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D014599:Uterus / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*
D004967:Estrogens; D013267:Stilbenes; D002996:Clomiphene; D012710:Serum Albumin, Bovine; D011374:Progesterone; D004958:Estradiol; D009594:Nitromifene; D004247:DNA; D004964:Estriol; C037749:triphenylethylene