Excess expression of uterine ribosomal protein genes P2 and S25 during the "implantation window" in the rat.

OBJECTIVE: The present study describes the isolation of "implantation-related" uterine cDNA clones. It further describes their temporal and spatial expression and their identification as the messengers for two ribosomal proteins: RP2 and RS25. METHODS: Libraries of cDNA, representing spayed rats treated with progesterone for 3 consecutive days and with estrogen for either 12 or 36 hours, were screened using homologous and heterologous probes. Two cDNA clones showing differential intensity of the signal were sequenced, the timing of their expression was analyzed by Northern analysis, and their spatial expression was visualized by in situ hybridization. RESULTS: The steady-state level of RP2 mRNA was temporally and spatially controlled by estrogen and progesterone. Whereas estrogen, alone or in combination with progesterone, stimulated this gene, the spatial distribution of the activation was different. Estradiol alone directed RP2 expression to the endometrial-myometrial border, whereas combined treatment increased epithelial staining and directed heavy expression to the stratum vasculare. In normal pregnancy, during the implantation-window period, RP2 was mainly expressed on the mesometrial side, with much less staining on the antimesometrial side. The steady-state levels of the RS25 messenger were elevated by estrogen alone or in combination with progesterone and were confined to the uterine epithelium. RS25 mRNA was evenly distributed throughout the uterine stroma during implantation. CONCLUSION: A developmental pattern of expression of RP2 is reported that corresponds temporally with the primary decidual response but is spatially expressed at the site of the secondary response.

Inhibition of decidual induction in rats by clomiphene and tamoxifen.

The objective of this study was to characterize the estrogen action that confers endometrial sensitization to nontraumatic deciduogenic stimuli by use of antiestrogens. Tamoxifen, ethamoxytriphetol, and clomiphene and its two component enantiomers inhibited decidual induction in pseudopregnant rats when administered 17 h before pyrathiazine. Unexpectedly, clomiphene (250 micrograms/rat) and tamoxifen (25 micrograms/rat) proved inhibitory at all times up to and including the time of induction. Clomiphene, administered in the hours preceding decidual induction, inhibited the increase of ornithine decarboxylase activity, which normally marks the end of the induction phase. Clomiphene had no inhibitory effect on the availability or receptor binding of progesterone. Clomiphene also inhibited implantation of blastocysts when administered at the time of their adherence to the uterus. The inhibition by antiestrogens of decidual induction could not be explained on the basis of the current understanding of mechanisms of estrogen action. The discrepancies were that no latent period between the time of antiestrogen administration and decidual induction was observed and no difference was observed in the inhibitory activities of the isomers of clomiphene.