TRANSFORMING-GROWTH-FACTOR BETA-1 IN THE HUMAN ENDOMETRIUM - CYCLIC VARIATION, INCREASED EXPRESSION BY ESTRADIOL AND PROGESTERONE, AND REGULATION OF PLASMINOGEN ACTIVATORS AND PLASMINOGEN-ACTIVATOR INHIBITOR-1

The purpose of this study was to identify cyclic variations and hormon al regulation of endometrial transforming growth factor beta 1 (TGF be ta 1) mRNA. Regulation of the plasminogen-activating system was also e xamined, since it is involved in activation of latent TGF beta s. We m easured TGF beta 1 mRNA in 51 normal endometrial samples by Northern b lot and densitometric scanning of autoradiograms. Each value was relat ed to the corresponding beta-actin value to allow quantitative evaluat ion. TGF beta 1 mRNA was higher in the mid and late secretory and mens trual phases than in the earlier parts of the cycle. This pattern impl ies progesterone dependence. The content of TGF beta 1 mRNA in endomet rial tissue explants obtained in the proliferative phase was significa ntly increased after stimulation for 4 days with estradiol + progester one in vitro. Both TGF beta 1 and estradiol + progesterone increased t he content of plasminogen activator inhibitor-1 mRNA and protein in pr imary cultures of endometrial stromal cells. Conditioned-medium concen trations of urokinase plasminogen activator (u-PA) were increased by T GF beta 1, but decreased by estradiol + progesterone. This effect of e stradiol + progesterone results from increased internalization and deg radation of u-PA secondary to up-regulation of the cell surface recept or for u-PA by progesterone (Casslen et al., JCEM 1995; 80: 2776-2784) . Increased extracellular u-PA in response to TGF beta 1 exposure was thus in concordance with an unchanged amount of available u-PA recepto rs on the cell surface. The activation mechanism of latent TGF beta in volves u-PA activity; since u-PA activity is reduced in the secretory endometrium, we suggest that although TGF beta 1 mRNA is increased in the mid and late secretory phase, TGF beta s are mainly in their laten t form until the premenstrual rise in u-PA activity stimulates activat ion. TGF beta may promote capillary growth during endometrial regenera tion.