PARACRINE INDUCERS OF UTERINE ENDOMETRIAL SPERMIDINE SPERMINE N-1-ACETYLTRANSFERASE GENE-EXPRESSION DURING EARLY-PREGNANCY IN THE PIG/

The endogenous factors that underlie the transient induction of the ge ne encoding spermidine/spermine N-1-acetyltransferase (SSAT), the rate -limiting enzyme in cellular polyamine catabolism, in pig uterine endo metrium during periimplantation are not known. The present study exami ned a number of peptide growth factors and regulatory molecules that a re present within the uterine environment at early pregnancy, coincide nt with maximal SSAT gene expression, for their ability to manifest en dogenous SSAT gene-inducing activity. Basal SSAT expression in luminal epithelial cells was higher (p < 0.01) than that for glandular epithe lial (GE) or stromal (ST) cells. Recombinant human insulin-like growth factor-I (IGF-I; 50 ng/ml) had no effect on steady-state SSAT mRNA le vels, but it increased mitogenesis in all three cell types. In contras t, ICF-I caused a marked induction (p < 0.01) of SSAT mRNA levels in t he human endometrial carcinoma cell line Hec-1-A. Uterine explants inc ubated with interleukin-6, transforming growth factor alpha, epidermal growth factor (each at 1, 10, and 100 ng/ml), retinoic acid and retin ol (each at 0.01, 0.1, and 1 mu M), and estradiol-17 beta (10 nM) had SSAT mRNA levels similar to controls. By contrast, leukemia inhibitory factor (LIF; at 10 and 100 ng/ml) caused a modest, but significant (p < 0.05), increase in SSAT mRNA levels over those of untreated explant s. This effect of LIF, however, did not approach the level of inductio n observed in CE or ST cells after addition of medium conditioned by D ay 12 or 17 porcine conceptuses and in endometrial explants supplement ed with medium conditioned by Day 21 porcine conceptuses or a continuo us cell line (Jag-1) derived from Day 14 porcine trophoblast. We sugge st that transient induction of endometrial SSAT gene expression at imp lantation is mediated by the functional interactions of specific conce ptus-derived regulatory factors, distinct from estrogen, with endometr ial-derived factor(s) such as LIF. These complex interactions are prob ably requisite for the transient, yet dramatic, induction of SSAT gene expression and may be critical for successful implantation.